4-Aminopyridine: One of the POTASSIUM CHANNEL BLOCKERS, with secondary effect on calcium currents, which is used mainly as a research tool and to characterize channel subtypes.Aminopyridines: Pyridines substituted in any position with an amino group. May be hydrogenated, but must retain at least one double bond.Potassium Channel Blockers: A class of drugs that act by inhibition of potassium efflux through cell membranes. Blockade of potassium channels prolongs the duration of ACTION POTENTIALS. They are used as ANTI-ARRHYTHMIA AGENTS and VASODILATOR AGENTS.Tetraethylammonium: A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)Tetraethylammonium CompoundsPotassium Channels: Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).Potassium Channels, Voltage-Gated: Potassium channel whose permeability to ions is extremely sensitive to the transmembrane potential difference. The opening of these channels is induced by the membrane depolarization of the ACTION POTENTIAL.Potassium: An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.Charybdotoxin: A 37-amino acid residue peptide isolated from the scorpion Leiurus quinquestriatus hebraeus. It is a neurotoxin that inhibits calcium activated potassium channels.Action Potentials: Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.Patch-Clamp Techniques: An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.Electrophysiology: The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.Delayed Rectifier Potassium Channels: A group of slow opening and closing voltage-gated potassium channels. Because of their delayed activation kinetics they play an important role in controlling ACTION POTENTIAL duration.Kv1.5 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that conducts a delayed rectifier current. It contributes to ACTION POTENTIAL repolarization of MYOCYTES in HEART ATRIA.Elapid Venoms: Venoms from snakes of the family Elapidae, including cobras, kraits, mambas, coral, tiger, and Australian snakes. The venoms contain polypeptide toxins of various kinds, cytolytic, hemolytic, and neurotoxic factors, but fewer enzymes than viper or crotalid venoms. Many of the toxins have been characterized.Barium Compounds: Inorganic compounds that contain barium as an integral part of the molecule.Neuromuscular Depolarizing Agents: Drugs that interrupt transmission at the skeletal neuromuscular junction by causing sustained depolarization of the motor end plate. These agents are primarily used as adjuvants in surgical anesthesia to cause skeletal muscle relaxation.Apamin: A highly neurotoxic polypeptide from the venom of the honey bee (Apis mellifera). It consists of 18 amino acids with two disulfide bridges and causes hyperexcitability resulting in convulsions and respiratory paralysis.Barium: An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous.Tetrodotoxin: An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction.Electric Conductivity: The ability of a substrate to allow the passage of ELECTRONS.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Cesium: A member of the alkali metals. It has an atomic symbol Cs, atomic number 50, and atomic weight 132.91. Cesium has many industrial applications, including the construction of atomic clocks based on its atomic vibrational frequency.Glyburide: An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.Quinidine: An optical isomer of quinine, extracted from the bark of the CHINCHONA tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular ACTION POTENTIALS, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission.Potassium Channels, Calcium-Activated: Potassium channels whose activation is dependent on intracellular calcium concentrations.Kv1.4 Potassium Channel: A fast inactivating subtype of shaker potassium channels that contains two inactivation domains at its N terminus.Scorpion Venoms: Venoms from animals of the order Scorpionida of the class Arachnida. They contain neuro- and hemotoxins, enzymes, and various other factors that may release acetylcholine and catecholamines from nerve endings. Of the several protein toxins that have been characterized, most are immunogenic.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.Shaw Potassium Channels: A shaker subfamily that is prominently expressed in NEURONS and are necessary for high-frequency, repetitive firing of ACTION POTENTIALS.Electric Stimulation: Use of electric potential or currents to elicit biological responses.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Ion Channel Gating: The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.Quinine: An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Kv1.1 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is commonly mutated in human episodic ATAXIA and MYOKYMIA.Hippocampus: A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.Shab Potassium Channels: A subfamily of shaker potassium channels that shares homology with its founding member, Shab protein, Drosophila. They regulate delayed rectifier currents in the NERVOUS SYSTEM of DROSOPHILA and in the SKELETAL MUSCLE and HEART of VERTEBRATES.Kv1.2 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is selectively inhibited by a variety of SCORPION VENOMS.Endothelium-Dependent Relaxing Factors: Paracrine substances produced by the VASCULAR ENDOTHELIUM with VASCULAR SMOOTH MUSCLE relaxation (VASODILATION) activities. Several factors have been identified, including NITRIC OXIDE and PROSTACYCLIN.Synaptic Transmission: The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.Convulsants: Substances that act in the brain stem or spinal cord to produce tonic or clonic convulsions, often by removing normal inhibitory tone. They were formerly used to stimulate respiration or as antidotes to barbiturate overdose. They are now most commonly used as experimental tools.Pyridostigmine Bromide: A cholinesterase inhibitor with a slightly longer duration of action than NEOSTIGMINE. It is used in the treatment of myasthenia gravis and to reverse the actions of muscle relaxants.Carbohydrate Sequence: The sequence of carbohydrates within POLYSACCHARIDES; GLYCOPROTEINS; and GLYCOLIPIDS.Microelectrodes: Electrodes with an extremely small tip, used in a voltage clamp or other apparatus to stimulate or record bioelectric potentials of single cells intracellularly or extracellularly. (Dorland, 28th ed)Shaker Superfamily of Potassium Channels: Voltage-gated potassium channels whose primary subunits contain six transmembrane segments and form tetramers to create a pore with a voltage sensor. They are related to their founding member, shaker protein, Drosophila.Tubocurarine: A neuromuscular blocker and active ingredient in CURARE; plant based alkaloid of Menispermaceae.Shal Potassium Channels: A shaker subfamily of potassium channels that participate in transient outward potassium currents by activating at subthreshold MEMBRANE POTENTIALS, inactivating rapidly, and recovering from inactivation quickly.Acetylcholine: A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.Vasodilation: The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.Cromakalim: A potassium-channel opening vasodilator that has been investigated in the management of hypertension. It has also been tried in patients with asthma. (Martindale, The Extra Pharmacopoeia, 30th ed, p352)Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position.Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016).QuinoxalinesPulmonary Stretch Receptors: Stretch receptors found in the bronchi and bronchioles. Pulmonary stretch receptors are sensors for a reflex which stops inspiration. In humans, the reflex is protective and is probably not activated during normal respiration.Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to CADMIUM POISONING.Evoked Potentials: Electrical responses recorded from nerve, muscle, SENSORY RECEPTOR, or area of the CENTRAL NERVOUS SYSTEM following stimulation. They range from less than a microvolt to several microvolts. The evoked potential can be auditory (EVOKED POTENTIALS, AUDITORY), somatosensory (EVOKED POTENTIALS, SOMATOSENSORY), visual (EVOKED POTENTIALS, VISUAL), or motor (EVOKED POTENTIALS, MOTOR), or other modalities that have been reported.Large-Conductance Calcium-Activated Potassium Channels: A major class of calcium activated potassium channels whose members are voltage-dependent. MaxiK channels are activated by either membrane depolarization or an increase in intracellular Ca(2+). They are key regulators of calcium and electrical signaling in a variety of tissues.Neuromuscular Junction: The synapse between a neuron and a muscle.Potassium Channels, Tandem Pore Domain: Potassium channels that contain two pores in tandem. They are responsible for baseline or leak currents and may be the most numerous of all K channels.Pinacidil: A guanidine that opens POTASSIUM CHANNELS producing direct peripheral vasodilatation of the ARTERIOLES. It reduces BLOOD PRESSURE and peripheral resistance and produces fluid retention. (Martindale The Extra Pharmacopoeia, 31st ed)Pyramidal Cells: Projection neurons in the CEREBRAL CORTEX and the HIPPOCAMPUS. Pyramidal cells have a pyramid-shaped soma with the apex and an apical dendrite pointed toward the pial surface and other dendrites and an axon emerging from the base. The axons may have local collaterals but also project outside their cortical region.Polymyxins: Basic lipopeptide antibiotic group obtained from Bacillus polymyxa. They affect the cell membrane by detergent action and may cause neuromuscular and kidney damage. At least eleven different members of the polymyxin group have been identified, each designated by a letter.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs.Vasodilator Agents: Drugs used to cause dilation of the blood vessels.Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.Kinetics: The rate dynamics in chemical or physical systems.Potassium Chloride: A white crystal or crystalline powder used in BUFFERS; FERTILIZERS; and EXPLOSIVES. It can be used to replenish ELECTROLYTES and restore WATER-ELECTROLYTE BALANCE in treating HYPOKALEMIA.Nerve Endings: Branch-like terminations of NERVE FIBERS, sensory or motor NEURONS. Endings of sensory neurons are the beginnings of afferent pathway to the CENTRAL NERVOUS SYSTEM. Endings of motor neurons are the terminals of axons at the muscle cells. Nerve endings which release neurotransmitters are called PRESYNAPTIC TERMINALS.Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent.Heart Ventricles: The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation.FMRFamide: A molluscan neuroactive peptide which induces a fast excitatory depolarizing response due to direct activation of amiloride-sensitive SODIUM CHANNELS. (From Nature 1995; 378(6558): 730-3)Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.Vasoconstriction: The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE.Heart: The hollow, muscular organ that maintains the circulation of the blood.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or "seizure disorder."Ventricular Function: The hemodynamic and electrophysiological action of the HEART VENTRICLES.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Sodium: A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.Neurotransmitter Agents: Substances used for their pharmacological actions on any aspect of neurotransmitter systems. Neurotransmitter agents include agonists, antagonists, degradation inhibitors, uptake inhibitors, depleters, precursors, and modulators of receptor function.Carbenoxolone: An agent derived from licorice root. It is used for the treatment of digestive tract ulcers, especially in the stomach. Antidiuretic side effects are frequent, but otherwise the drug is low in toxicity.Epilepsy: A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313)Excitatory Amino Acid Antagonists: Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.OxadiazolesBicuculline: An isoquinoline alkaloid obtained from Dicentra cucullaria and other plants. It is a competitive antagonist for GABA-A receptors.Carbohydrate Conformation: The characteristic 3-dimensional shape of a carbohydrate.Muscle, Smooth: Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)
(1/1089) Characterization of K+ currents underlying pacemaker potentials of fish gonadotropin-releasing hormone cells.

Endogenous pacemaker activities are important for the putative neuromodulator functions of the gonadotropin-releasing hormone (GnRH)-immunoreactive terminal nerve (TN) cells. We analyzed several types of voltage-dependent K+ currents to investigate the ionic mechanisms underlying the repolarizing phase of pacemaker potentials of TN-GnRH cells by using the whole brain in vitro preparation of fish (dwarf gourami, Colisa lalia). TN-GnRH cells have at least four types of voltage-dependent K+ currents: 1) 4-aminopyridine (4AP)-sensitive K+ current, 2) tetraethylammonium (TEA)-sensitive K+ current, and 3) and 4) two types of TEA- and 4AP-resistant K+ currents. A transient, low-threshold K+ current, which was 4AP sensitive and showed significant steady-state inactivation in the physiological membrane potential range (-40 to -60 mV), was evoked from a holding potential of -100 mV. This current thus cannot contribute to the repolarizing phase of pacemaker potentials. TEA-sensitive K+ current evoked from a holding potential of -100 mV was slowly activating, long lasting, and showed comparatively low threshold of activation. This current was only partially inactivated at steady state of -60 to -40 mV, which is equivalent to the resting membrane potential. TEA- and 4AP-resistant sustained K+ currents were evoked from a holding potential of -100 mV and were suggested to consist of two types, based on the analysis of activation curves. From the inactivation and activation curves, it was suggested that one of them with low threshold of activation may be partly involved in the repolarizing phase of pacemaker potentials. Bath application of TEA together with tetrodotoxin reversibly blocked the pacemaker potentials in current-clamp recordings. We conclude that the TEA-sensitive K+ current is the most likely candidate that contributes to the repolarizing phase of the pacemaker potentials of TN-GnRH cells.  (+info)

(2/1089) Presynaptic action of adenosine on a 4-aminopyridine-sensitive current in the rat carotid body.

1. Plasma adenosine concentration increases during hypoxia to a level that excites carotid body chemoreceptors by an undetermined mechanism. We have examined this further by determining the electrophysiological responses to exogenous adenosine of sinus nerve chemoafferents in vitro and of whole-cell currents in isolated type I cells. 2. Steady-state, single-fibre chemoafferent discharge was increased approximately 5-fold above basal levels by 100 microM adenosine. This adenosine-stimulated discharge was reversibly and increasingly reduced by methoxyverapamil (D600, 100 microM), by application of nickel chloride (Ni2+, 2 mM) and by removal of extracellular Ca2+. These effects strongly suggest a presynaptic, excitatory action of adenosine on type I cells of the carotid body. 3. Adenosine decreased whole-cell outward currents at membrane potentials above -40 mV in isolated type I cells recorded during superfusion with bicarbonate-buffered saline solution at 34-36 C. This effect was reversible and concentration dependent with a maximal effect at 10 microM. 4. The degree of current inhibition induced by 10 microM adenosine was voltage independent (45.39 +/- 2. 55 % (mean +/- s.e.m.) between -40 and +30 mV) and largely ( approximately 75 %), but not entirely, Ca2+ independent. 4-Aminopyridine (4-AP, 5 mM) decreased the amplitude of the control outward current by 80.60 +/- 3.67 % and abolished the effect of adenosine. 5. Adenosine was without effect upon currents near the resting membrane potential of approximately -55 mV and did not induce depolarization in current-clamp experiments. 6. We conclude that adenosine acts to inhibit a 4-AP-sensitive current in isolated type I cells of the rat carotid body and suggest that this mechanism contributes to the chemoexcitatory effect of adenosine in the whole carotid body.  (+info)

(3/1089) Contribution of delayed rectifier potassium currents to the electrical activity of murine colonic smooth muscle.

1. We used intracellular microelectrodes to record the membrane potential (Vm) of intact murine colonic smooth muscle. Electrical activity consisted of spike complexes separated by quiescent periods (Vm approximately -60 mV). The spike complexes consisted of about a dozen action potentials of approximately 30 mV amplitude. Tetraethylammonium (TEA, 1-10 mM) had little effect on the quiescent periods but increased the amplitude of the action potential spikes. 4-Aminopyridine (4-AP, >= 5 mM) caused continuous spiking. 2. Voltage clamp of isolated myocytes identified delayed rectifier K+ currents that activated rapidly (time to half-maximum current, 11.5 ms at 0 mV) and inactivated in two phases (tauf = 96 ms, taus = 1.5 s at 0 mV). The half-activation voltage of the permeability was -27 mV, with significant activation at -50 mV. 3. TEA (10 mM) reduced the outward current at potentials positive to 0 mV. 4-AP (5 mM) reduced the early current but increased outward current at later times (100-500 ms) consistent with block of resting channels relieved by depolarization. 4-AP inhibited outward current at potentials negative to -20 mV, potentials where TEA had no effect. 4. Qualitative PCR amplification of mRNA identified transcripts encoding delayed rectifier K+ channel subunits Kv1.6, Kv4.1, Kv4.2, Kv4.3 and the Kvbeta1.1 subunit in murine colon myocytes. mRNA encoding Kv 1.4 was not detected. 5. We find that TEA-sensitive delayed rectifier currents are important determinants of action potential amplitude but not rhythmicity. Delayed rectifier currents sensitive to 4-AP are important determinants of rhythmicity but not action potential amplitude.  (+info)

(4/1089) Calcium responses induced by acetylcholine in submucosal arterioles of the guinea-pig small intestine.

1. Calcium responses induced by brief stimulation with acetylcholine (ACh) were assessed from the fluorescence changes in fura-2 loaded submucosal arterioles of the guinea-pig small intestine. 2. Initially, 1-1.5 h after loading with fura-2 (fresh tissues), ACh increased [Ca2+]i in a concentration-dependent manner. This response diminished with time, and finally disappeared in 2-3 h (old tissues). 3. Ba2+ elevated [Ca2+]i to a similar extent in both fresh and old tissues. ACh further increased the Ba2+-elevated [Ca2+]i in fresh tissues, but reduced it in old tissues. Responses were not affected by either indomethacin or nitroarginine. 4. In fresh mesenteric arteries, mechanical removal of endothelial cells abolished the ACh-induced increase in [Ca2+]i, with no alteration of [Ca2+]i at rest and during elevation with Ba2+. 5. In the presence of indomethacin and nitroarginine, high-K+ solution elevated [Ca2+]i in both fresh and old tissues. Subsequent addition of ACh further increased [Ca2+]i in fresh tissues without changing it in old tissues. 6. Proadifen, an inhibitor of the enzyme cytochrome P450 mono-oxygenase, inhibited the ACh-induced changes in [Ca2+]i in both fresh and Ba2+-stimulated old tissues. It also inhibited the ACh-induced hyperpolarization. 7. In fresh tissues, the ACh-induced Ca2+ response was not changed by apamin, charybdotoxin (CTX), 4-aminopyridine (4-AP) or glibenclamide. In old tissues in which [Ca2+]i had previously been elevated with Ba2+, the ACh-induced Ca2+ response was inhibited by CTX but not by apamin, 4-AP or glibenclamide. 8. It is concluded that in submucosal arterioles, ACh elevates endothelial [Ca2+]i and reduces muscular [Ca2+]i, probably through the hyperpolarization of endothelial or smooth muscle membrane by activating CTX-sensitive K+ channels.  (+info)

(5/1089) Identification and characterization of multiple subtypes of muscarinic acetylcholine receptors and their physiological functions in canine hearts.

M2 receptors have long been believed to be the only functional subtype of muscarinic acetylcholine receptor (mAChR) in the heart, although recent studies have provided evidence for the presence of other subtypes. We performed a detailed study to clarify this issue. In the presence of tetramethylammonium (1 microM to 10 mM), a novel K+ current with both delayed rectifying and inward rectifying properties (IKTMA) was activated in single canine atrial myocytes. 4-Aminopyridine (0.05-2 mM) also induced a K+ current (IK4AP) with characteristics similar to but distinct from those of IKTMA. Both IKTMA and IK4AP were abolished by 1 microM atropine. IK4AP, but not IKTMA, was minimized by treatment with pertussis toxin. IKTMA was markedly decreased by 4-diphenylacetoxy-N-methylpiperidine methiodide (a selective antagonist for M3 subtype) but was not altered by pirenzepine (for M1), methoctramine (for M2), and tropicamide (for M4). Tropicamide substantially reduced IK4AP, but the antagonists for other mAChR subtypes had no effects on IK4AP. By comparison, IKACh (ACh-induced K+ current) was significantly depressed by methoctramine but was unaltered by other antagonists. Results from displacement binding of [methyl-3H]N-scopolamine methyl chloride with pirenzepine, methoctramine, 4-diphenylacetoxy-N-methylpiperidine methiodide, or tropicamide revealed the coexistence of multiple mAChR subtypes in canine atrium. Cloning of cDNA fragments and detection of mRNAs coding for M2, M3, and M4 provided further supporting evidence. Our results suggest that 1) multiple subtypes of mAChRs (M2/M3/M4) coexist in the dog heart and 2) different subtypes of mAChRs are coupled to different K+ channels. Our findings represent the first functional evidence for the physiological role of cardiac M3 and M4 receptors.  (+info)

(6/1089) Transient potassium currents regulate the discharge patterns of dorsal cochlear nucleus pyramidal cells.

Pyramidal cells in the dorsal cochlear nucleus (DCN) show three distinct temporal discharge patterns in response to sound: "pauser," "buildup," and "chopper." Similar discharge patterns are seen in vitro and depend on the voltage from which the cell is depolarized. It has been proposed that an inactivating A-type K+ current (IKI) might play a critical role in generating the three different patterns. In this study we examined the characteristics of transient currents in DCN pyramidal cells to evaluate this hypothesis. Morphologically identified pyramidal cells in rat brain slices (P11-P17) exhibited the three voltage-dependent discharge patterns. Two inactivating currents were present in outside-out patches from pyramidal cells: a rapidly inactivating (IKIF, tau approximately 11 msec) current insensitive to block by tetraethylammonium (TEA) and variably blocked by 4-aminopyridine (4-AP) with half-inactivation near -85 mV, and a slowly inactivating TEA- and 4-AP-sensitive current (IKIS, tau approximately 145 msec) with half-inactivation near -35 mV. Recovery from inactivation at 34 degrees C was described by a single exponential with a time constant of 10-30 msec, similar to the rate at which first spike latency increases with the duration of a hyperpolarizing prepulse. Acutely isolated cells also possessed a rapidly activating (<1 msec at 22 degrees C) transient current that activated near -45 mV and showed half-inactivation near -80 mV. A model demonstrated that the deinactivation of IKIF was correlated with the discharge patterns. Overall, the properties of the fast inactivating K+ current were consistent with their proposed role in shaping the discharge pattern of DCN pyramidal cells.  (+info)

(7/1089) On the mechanism of histaminergic inhibition of glutamate release in the rat dentate gyrus.

1. Histaminergic depression of excitatory synaptic transmission in the rat dentate gyrus was investigated using extracellular and whole-cell patch-clamp recording techniques in vitro. 2. Application of histamine (10 microM, 5 min) depressed synaptic transmission in the dentate gyrus for 1 h. This depression was blocked by the selective antagonist of histamine H3 receptors, thioperamide (10 microM). 3. The magnitude of the depression caused by histamine was inversely related to the extracellular Ca2+ concentration. Application of the N-type calcium channel blocker omega-conotoxin (0. 5 or 1 microM) or the P/Q-type calcium channel blocker omega-agatoxin (800 nM) did not prevent depression of synaptic transmission by histamine. 4. The potassium channel blocker 4-aminopyridine (4-AP, 100 microM) enhanced synaptic transmission and reduced the depressant effect of histamine (10 microM). 4-AP reduced the effect of histamine more in 2 mM extracellular calcium than in 4 mM extracellular calcium. 5. Histamine (10 microM) did not affect the amplitude of miniature excitatory postsynaptic currents (mEPSCs) and had only a small effect on their frequency. 6. Histaminergic depression was not blocked by an inhibitor of serine/threonine protein kinases, H7 (100 microM), or by an inhibitor of tyrosine kinases, Lavendustin A (10 microM). 7. Application of adenosine (20 microM) or the adenosine A1 agonist N6-cyclopentyladenosine (CPA, 0.3 microM) completely occluded the effect of histamine (10 microM). 8. We conclude that histamine, acting on histamine H3 receptors, inhibits glutamate release by inhibiting presynaptic calcium entry, via a direct G-protein-mediated inhibition of multiple calcium channels. Histamine H3 receptors and adenosine A1 receptors act upon a common final effector to cause presynaptic inhibition.  (+info)

(8/1089) The cAMP transduction cascade mediates the PGE2-induced inhibition of potassium currents in rat sensory neurones.

1. The role of the cyclic AMP (cAMP) transduction cascade in mediating the prostaglandin E2 (PGE2)-induced decrease in potassium current (IK) was investigated in isolated embryonic rat sensory neurones using the whole-cell patch-clamp recording technique. 2. Exposure to 100 microM chlorophenylthio-adenosine cyclic 3', 5'-monophosphate (cpt-cAMP) or 1 microM PGE2 caused a slow suppression of the whole-cell IK by 34 and 36 %, respectively (measured after 20 min), without a shift in the voltage dependence of activation for this current. Neither of these agents altered the shape of the voltage-dependent inactivation curve indicating that the suppression of IK did not result from alterations in the inactivation properties. 3. To determine whether the PGE2-mediated suppression of IK depended on activation of the cAMP pathway, cells were exposed to this prostanoid in the presence of the protein kinase A (PKA) inhibitor, PKI. The PGE2-induced suppression of IK was prevented by PKI. In the absence of PGE2, PKI had no significant effect on the magnitude of IK. 4. Results obtained from protocols using different conditioning prepulse voltages indicated that the extent of cpt-cAMP- and PGE2-mediated suppression of IK was independent of the prepulse voltage. The subtraction of control and treated currents revealed that the cpt-cAMP- and PGE2-sensitive currents exhibited little time-dependent inactivation. Taken together, these results suggest that the modulated currents may be delayed rectifier-like IK. 5. Exposure to the inhibitors of IK, tetraethylammonium (TEA) or 4-aminopyridine (4-AP), reduced the control current elicited by a voltage step to +60 mV by 40-50 %. In the presence of 10 mM TEA, treatment with cpt-cAMP did not result in any further inhibition of IK. In contrast, cpt-cAMP reduced IK by an additional 25-30 % in the presence of 1 mM 4-AP. This effect was independent of the conditioning prepulse voltage. 6. These results establish that PGE2 inhibits an outward IK in sensory neurones via activation of PKA and are consistent with the idea that the PGE2-mediated sensitization of sensory neurones results, in part, from an inhibition of delayed rectifier-like IK.  (+info)

*  4-Aminopyridine
"Aminopyridines for symptomatic treatment in multiple sclerosis". Cochrane Database Syst Rev (4): CD001330. doi:10.1002/14651858 ... Octopus Envenomations at eMedicine.com Wu, ZZ; Li, DP; Chen, SR; Pan, HL (2009). "Aminopyridines Potentiate Synaptic and ... The use of 4-aminopyridine in bird control has been criticized by the Humane Society of the United States. Fampridine has been ... 4-Aminopyridine is also used under the trade name Avitrol as 0.5% or 1% in bird control bait. It causes convulsions and, ...
*  Centre for Human Reproductive Science
Gu Y, Kirkman-Brown JC, Korchev Y, Barratt CL, Publicover SJ (October 2004). "Multi-state, 4-aminopyridine-sensitive ion ...
*  Xylazine
The duration of effects in animals lasts up to 4 hours. Xylazine users are more likely to be male, under the age of 30, living ... 11 (4): 295-313. doi:10.1111/j.1365-2885.1988.tb00189.x. PMID 3062194. Xylazine at drugs.com by Patricia M. Dowling & Johann ( ... Combining yohimbine and 4-aminopyridine in an effort to antagonize xylazine is superior as compared to the administration of ... 4 (2): 128-34. PMID 14506588. Veilleux-Lemieux, D; Castel, A; Carrier, D; Beaudry, F; Vachon, P (September 2013). " ...
*  N-(p-amylcinnamoyl)anthranilic acid
"4-Aminopyridine and the early outward current of sheep cardiac Purkinje fibers". J Gen Physiol 1979;73:139-157. Zygmunt AC, ... Li GR, Feng J, Wang Z, Fermini B, Nattel S. "Comparative mechanisms of 4-aminopyridine-resistant Ito in human and rabbit atrial ...
*  4-Pyridylnicotinamide
... (4-PNA), also known as N-(pyridin-4-yl)nicotinamide, is a kinked dipodal dipyridine which was originally ... Kraft, P. E.; Laduca, R. L. (2012). "Catena-Poly\\tetra-μ-benzoato-κ8O:O′-dicopper(II)]-μ-\N-(pyridin-4-yl)nicotinamide]-κ2N:N ... It is synthesized through the reaction of nicotinoyl chloride and 4-aminopyridine. Gardner, T. S.; Wenis, E.; Lee, J. (1954). " ... dibenzoato-κ2O-copper(II)]-μ-\N-(pyridin-4-yl)nicotinamide]-κ2N:N′]". Acta Crystallographica Section E. 68 (8): m1049. doi: ...
*  Amifampridine
Solari, A.; Uitdehaag, B.; Giuliani, G.; Pucci, E.; Taus, C. (2002). "Aminopyridines for symptomatic treatment in multiple ... Sedehizadeh, S; Keogh, M; Maddison, P (2012). "The use of aminopyridines in neurological disorders". Clinical neuropharmacology ... 3,4-DAP was discovered in Scotland in the 1970s, and doctors in Sweden first showed its use in LEMS in the 1980s. In the 1990s ... A 2011 Cochrane review compared the cost of the 3,4-DAP and 3,4-DAPP in the UK and found an average price for 3,4-DAP base of £ ...
*  Paroxysmal depolarizing shift
http://serbiosoc.org.rs/arch_old/VOL62/SVESKA_4/21%20-%20Pathak.pdf Angstadt, JD; Choo, JJ (1996). "Sodium-dependent plateau ... 2010), MODULATION OF NICKEL-INDUCED BURSTING WITH 4-AMINOPYRIDINE IN LEECH RETZIUS NERVE CELLS. ...
*  Ipidacrine
4 (3): 247. doi:10.1111/j.1527-3458.1998.tb00067.x. Damulin, IV; Stepkina, DA; Lokshina, AB (2011). "Neuromidin in mixed ... 111 (4 Pt 2): 23-7. PMID 23120773. Onodera, K; Kojima, J; Wachi, M (1998). "Ipidacrine (NIK-247), a novel antidementia, rapidly ... This compound is a derivative of 4-aminopyridine and is structurally similar to tacrine. Ipidacrine is a reversible ...
*  Feral pigeon
DRC-1339 is limited to USDA use only, while 4-AP is a restricted-use pesticide, for use only by licensed applicators. The use ... Retrieved 4 January 2017. Levi, Wendell (1977). The Pigeon. Sumter, S.C.: Levi Publishing Co, Inc. ISBN 0-85390-013-2. Johnston ... 14 (4): 251-255. doi:10.1089/vbz.2011.0943. PMID 24661012. Osman, Kamelia M.; Mehrez, Mona; Erfan, Ahmed M.; Al Atfeehy, ... Retrieved January 4, 2017. Reinoso, V.; Katani, R.; Barbato, G. F. (2007). "Nicarbazin reduces egg production and fertility in ...
*  Tetraethylammonium
Apr;19(4):497-503. J. P. Hendrix (1949. "Neostigmine as antidote to Etamon®." JAMA 139(11) 733-734. S. W. Hoobler, G. K. Moe ... "Ion dependence of the release of noradrenaline by tetraethylammonium and 4-aminopyridine from cat splenic slices." Br. J. ...
*  Neurotoxin
17 (4): 151-55. doi:10.1016/0166-2236(94)90092-2. Ahasan, H A M N, A. A. Mamun, S. R. Karim, M. A. Baker, E. A. Gazi, and C. S ... 50 (4): 1117-122. doi:10.1111/j.1471-4159.1988.tb10581.x. Buzanska, L.; Zablocka, B.; Dybel, A.; Domanska-Janik, K.; Albrecht, ... 24 (4): 512-18. doi:10.1111/j.1530-0277.2000.tb02019.x. Hensley, K (1994). "A Model for β-Amyloid Aggregation and Neurotoxicity ... 19 (4): 488-96. doi:10.1002/(sici)1097-4598(199604)19:4. 3.0.co;2-8. Rothman, S.; Thurston, J.; Hauhart, R. (1987). "Delayed ...
*  Vinpocetine
... has also been shown to abolish [3H]Glu release after in vivo exposure to 4-aminopyridine (4-AP) which suggests an ... with full remission typically occurring within 3-4 weeks. Vinpocetine has been reported to have cerebral blood-flow enhancing ... "Vinpocetine inhibits glutamate release induced by the convulsive agent 4-aminopyridine more potently than several antiepileptic ...
*  KCNB1
123 (4): 387-400. doi:10.1085/jgp.200308976. PMC 2217458 . PMID 15024041. Thébaud B, Michelakis ED, Wu XC, Moudgil R, Kuzyk M, ... 57 (4): 473-508. doi:10.1124/pr.57.4.10. PMID 16382104. Shah NH, Aizenman E (February 2014). "Voltage-gated potassium channels ... 4 (1): 60-70. doi:10.1007/s11481-008-9106-6. PMC 3974578 . PMID 18459047. Kondratskyi A, Kondratska K, Skryma R, Prevarskaya N ... 8 (4): e2737. doi:10.1038/cddis.2017.160. Swartz KJ (February 2007). "Tarantula toxins interacting with voltage sensors in ...
*  Dizocilpine
28 (4): 539-46. doi:10.1002/ana.410280411. PMID 2252365. Faden AI, Lemke M, Simon RP, Noble LJ (1988). "N-methyl-D-aspartate ... 4 (4): 281-6. doi:10.1080/13651500050517830. Basile AS, Huang JM, Xie C, Webster D, Berlin C, Skolnick P (December 1996). "N- ... 80 (1): 111-4. doi:10.1016/0304-3940(87)90505-2. PMID 2821457. Ramoa AS, Alkondon M, Aracava Y, et al. (July 1990). "The ... 35 (4): 407-14. doi:10.1016/0028-3908(96)00006-8. PMID 8793902. Iravani MM, Muscat R, Kruk ZL (June 1999). "MK-801 interaction ...
*  Fullerene chemistry
4-membered rings can be obtained by [2+2]cycloadditions for instance with benzyne. An example of a 1,3-dipolar cycloaddition to ... 199 (3-4): 373. Bibcode:1992CPL...199..373C. doi:10.1016/0009-2614(92)80134-W. Ohtsuki, T.; Ohno, K.; Shiga, K.; Kawazoe, Y.; ... The trimer has also been reported using 4-aminopyridine as catalyst (4% yield) and observed with scanning tunneling microscopy ... 4-cycloaddition of a fullerene". Journal of the Chemical Society, Perkin Transactions 2 (10): 2079. doi:10.1039/P29960002079. ...
*  Potassium channel
40 (4): 551-9. doi:10.1016/S0028-3908(00)00189-1. PMID 11249964. Kindler CH, Paul M, Zou H, Liu C, Winegar BD, Gray AT, Yost CS ... 8 (4): 345-52. doi:10.1007/s11910-008-0053-7. PMC 2587091 . PMID 18590620. Doyle DA, Morais Cabral J, Pfuetzner RA, Kuo A, ... 431 (7010): 830-4. Bibcode:2004Natur.431..830N. doi:10.1038/nature02943. PMID 15483608. Varma S, Rempe SB (Aug 2007). "Tuning ... doi:10.1007/978-4-319-21756-7_9. Rang, HP (2003). Pharmacology. Edinburgh: Churchill Livingstone. p. 60. ISBN 0-443-07145-4. ...
*  Besipirdine
As a member of the aminopyridine class, besipirdine enhances the release of acetylcholine by blocking M-channels, voltage-gated ... 300 (1-2): 71-4. doi:10.1016/0014-2999(96)00002-7. PMID 8741167. Francis, P. T.; Palmer, A. M.; Snape, M; Wilcock, G. K. (1999 ... Its N-despropyl metabolite, P86-7480, exhibits transient vasoconstrictor effects, producing a pressor effect of 16 ± 4 mm Hg ... Besipirdine (besipirdine hydrochloride, or HP749), an indole-substituted analog of 4-aminopyridine, is a nootropic drug ...
*  KCNC1
57 (4): 473-508. doi:10.1124/pr.57.4.10. PMID 16382104. Lien CC, Jonas P (March 2003). "Kv3 potassium conductance is necessary ... 57 (4): 473-508. doi:10.1124/pr.57.4.10. PMID 16382104. "Entrez Gene: KCNC1 potassium voltage-gated channel, Shaw-related ... The overlapping sensitivity of potassium current to both 0.5 mM TEA and 30 μM 4-AP strongly suggest an action on Kv3.1 subunits ... Kv3.1 currents in heterologous systems are highly sensitive to external tetraethylammonium (TEA) or 4-aminopyridine (4-AP) ( ...
*  C5H6N2
The molecular formula C5H6N2 may refer to: Aminopyridines 2-Aminopyridine 3-Aminopyridine 4-Aminopyridine Diazepines 1,2- ...
*  KCNC2
57 (4): 473-508. doi:10.1124/pr.57.4.10. PMID 16382104. Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, ... 4 (12): 711-5. doi:10.1007/BF00357794. PMID 8111118. Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, ... 57 (4): 473-508. doi:10.1124/pr.57.4.10. PMID 16382104. Kolodin YO (2008-04-27). "Ionic conductances underlying excitability in ... Kv3.2 currents in heterologous systems are highly sensitive to external tetraethylammonium (TEA) or 4-aminopyridine (4-AP) ( ...
*  Avicide
Commonly used avicides include strychnine, DRC-1339 (3-chloro-4-methylaniline hydrochloride, Starlicide) and CPTH (3-chloro-p- ... 4-aminopyridine). Chloralose is also used as an avicide. In the past, highly concentrated formulations of parathion in diesel ... 4-Aminopyridine Exposure of nontarget birds to DRC-1339 avicide in fall baited sunflower fields BIOONE Online Journals - BIOONE ...
*  Benign paroxysmal positional vertigo
131 (4): 438-44. doi:10.1016/j.otohns.2004.02.046. PMID 15467614. Cohen, HS (2004). "Side-lying as an alternative to the Dix- ... 139 (5 Suppl 4): S47-81. doi:10.1016/j.otohns.2008.08.022. PMID 18973840. Lay summary - AAO-HNS (2008-11-01). Dickson, Gretchen ... 25 (2): 130-4. doi:10.1097/00129492-200403000-00008. PMID 15021771. Buchholz, D. Heal Your Headache. New York:Workman ... and 4-aminopyridine for the treatment of episodic ataxia type 2 and both downbeat and upbeat nystagmus. These drug therapies ...
*  Ataxia
22 (4): 859-77, vii. doi:10.1016/j.cger.2006.06.011. PMID 17000340. Ilg W, Synofzik M, Brötz D, Burkard S, Giese MA, Schöls L ( ... 4 (6): 349-61. doi:10.1016/S1474-4422(05)70096-X. PMID 15907739. Moeller JJ, Macaulay RJ, Valdmanis PN, Weston LE, Rouleau GA, ... ISBN 0-87893-060-4. Fonteyn EM, Schmitz-Hübsch T, Verstappen CC, Baliko L, Bloem BR, Boesch S, Bunn L, Charles P, Dürr A, Filla ... 20 (4): 497-500. doi:10.1002/mds.20375. PMID 15645525. Schmitz TJ, O'Sullivan SB (2007). "Examination of Coordination". ...
*  List of types of poison
"4-Aminopyridine". pmep.cce.cornell.edu. Retrieved 2017-11-19. Toxicity Antibiotic. ...
*  List of MeSH codes (D02)
4,4'-(3-oxo-1,5-pentanediyl)bis(n,n-dimethyl-n-2-propenyl-), dibromide MeSH D02.092.146.325 --- p-dimethylaminoazobenzene MeSH ... 4,5-trisphosphate MeSH D02.033.800.519.400.700 --- phytic acid MeSH D02.033.800.609 --- mannitol MeSH D02.033.800.609.450 --- ... 4-nitrophenyl) ester MeSH D02.705.539.783 --- phorate MeSH D02.705.539.790 --- phosmet MeSH D02.705.539.900 --- temefos MeSH ... 4-nitrophenyl) ester MeSH D02.886.309.783 --- phorate MeSH D02.886.309.790 --- phosmet MeSH D02.886.309.900 --- temefos MeSH ...
*  List of extremely hazardous substances
4-nitrophenyl) O-phenyl ester Phosphoric acid, dimethyl 4-(methylthio)phenyl ester Phosphonothioic acid, O,O-dimethyl-S-(2- ... 4-(methylthio)phenyl) ester Phosphonothioic acid, methyl-, S-(2-(bis(1-methylethyl)amino)ethyl) O-ethyl ester Phosphonothioic ... 4'-amino- Propyleneimine Prothoate Pyrene Pyridine, 4-amino- Pyridine, 4-nitro-, 1-oxide Pyriminil Ricin Salcomine Sarin ... 4,5-dichloro-2-(trifluoromethyl)- Benzotrichloride Benzyl chloride Benzyl cyanide Bicyclo(2.2.1)heptane-2-carbonitrile Bis( ...
Rapid protium-deuterium exchange of 4-aminopyridines in neutral D2O under microwave irradiation  : Sussex Research Online  Rapid protium-deuterium exchange of 4-aminopyridines in neutral D2O under microwave irradiation : Sussex Research Online
4-Aminopyridines undergo surprisingly rapid and highly-selective H/D exchange at C-2 and C-6 in neutral D2O upon microwave ... Bagley, Mark C, Alnomsy, Ayed and Sharhan, Hussein I (2016) Rapid protium-deuterium exchange of 4-aminopyridines in neutral D2O ... Rapid protium-deuterium exchange of 4-aminopyridines in neutral D2O under microwave irradiation ... and C-substituted 4-aminopyridines and a ben-zofused (quinoline) analogue. ...
more infohttp://sro.sussex.ac.uk/62146/
Aminopyridines and Similarly Acting Drugs: Effects on Nerves, Muscles and Synapses - 1st Edition  Aminopyridines and Similarly Acting Drugs: Effects on Nerves, Muscles and Synapses - 1st Edition
Purchase Aminopyridines and Similarly Acting Drugs: Effects on Nerves, Muscles and Synapses - 1st Edition. Print Book & E-Book ... Aminopyridines and Synaptic Transmission. Lectures. General Principles of Synaptic Transmission. Effects of Aminopyridines on ... Clinical Applications of Aminopyridines. Lectures. Therapeutic Applications of Aminopyridines in Diseases of Neuromuscular ... Structure-Activity Relationships Amongst Aminopyridines. Aminopyridine as a tool to Investigate the Mechanism of Acetylcholine ...
more infohttps://www.elsevier.com/books/aminopyridines-and-similarly-acting-drugs/lechat/978-0-08-028000-4
3,4-Diaminopyridine, China 3,4-Diaminopyridine, 3,4-Diaminopyridine exporters, China 3,4-Diaminopyridine Suppliers - nwchemical  3,4-Diaminopyridine, China 3,4-Diaminopyridine, 3,4-Diaminopyridine exporters, China 3,4-Diaminopyridine Suppliers - nwchemical
4-Diaminopyridine Suppliers, provide quality 3,4-Diaminopyridine product and the products related with China 3,4- ... 2-methyl -3-amino pyridine. *• 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride ... 3,4-DAP;3,4-Pyridinediamine;4,5-Diaminopyridine;5-22-11-00266 (Beilstein Handbook Reference);BRN 0110232;Diamino-3,4 pyridine; ... Chinachemnet , Sign in , Join Now3,4-Diaminopyridine Manufacturers, China 3,4-Diaminopyridine Suppliers, China 3,4- ...
more infohttp://www.chinachemnet.com/38045/3,4-Diaminopyridine-1617563.html
Flow Chemistry Reactions 1  Flow Chemistry Reactions 1
The recipe is applicable to a wide range of aminopyridines and can be telescoped with an amide formation to obtain Imidazo[1,2- ... pyridine-2-carboxylic acids synthesis directly from condensation of substituted 2-aminopyridines and bromopyruvic acid. ... 4 - Hantzsch synthesis of pyrrole-3-carboxylic ester. This paper describes experimental conditions for a quick Hantzsch ... This paper describes a general method for the synthesis of bis-substituted 1,2,4-oxadiazoles in one continuous flow sequence. 1 ...
more infohttp://www.megantech.pl/en/top/flow-chemistry/flow-chemistry-reactions/
4-Aminopyridine - Wikipedia  4-Aminopyridine - Wikipedia
"Aminopyridines for symptomatic treatment in multiple sclerosis". Cochrane Database Syst Rev (4): CD001330. doi:10.1002/14651858 ... Octopus Envenomations at eMedicine.com Wu, ZZ; Li, DP; Chen, SR; Pan, HL (2009). "Aminopyridines Potentiate Synaptic and ... The use of 4-aminopyridine in bird control has been criticized by the Humane Society of the United States. Fampridine has been ... 4-Aminopyridine is also used under the trade name Avitrol as 0.5% or 1% in bird control bait. It causes convulsions and, ...
more infohttps://en.wikipedia.org/wiki/4-Aminopyridine
Prolonged Toxic Encephalopathy following Accidental 4-Aminopyridine Overdose  Prolonged Toxic Encephalopathy following Accidental 4-Aminopyridine Overdose
The 4-AP content of the pill that was ingested by the patient was at least 8 times greater (,80 mg) than the standard. The ... She was receiving 4-AP for more than 3 years. The symptoms started soon after the ingestion of a single pill that was supposed ... 4-Aminopyridine (4-AP) is a drug that is used to improve motor fatigue in patients suffering from multiple sclerosis (MS). ... 4-AP is a potassium channel-blocking drug. The prolongation of the action potential may facilitate calcium entry into the cell ...
more infohttps://www.hindawi.com/journals/crinm/2014/237064/
4-aminopyridine | definition of 4-aminopyridine by Medical dictionary  4-aminopyridine | definition of 4-aminopyridine by Medical dictionary
What is 4-aminopyridine? Meaning of 4-aminopyridine medical term. What does 4-aminopyridine mean? ... Looking for online definition of 4-aminopyridine in the Medical Dictionary? 4-aminopyridine explanation free. ... 4-aminopyridine. Also found in: Encyclopedia, Wikipedia. 4-aminopyridine. 1. a central nervous system stimulant and a ... The drug 4-aminopyridine partially restores some sensory and motor functions in one-third of patients who have been paralyzed ...
more infohttp://medical-dictionary.thefreedictionary.com/4-Aminopyridine
4-Aminopyridine treatment for chronic spinal cord injury  4-Aminopyridine treatment for chronic spinal cord injury
Until recently, I have been reluctant to post much about 4-aminopyridine (4-AP) or fampridine for three reasons. First, ... How should I ramp up on the dose of 4-AP to avoid side-effects when I start taking the drug? Experience in clinical trials of 4 ... What is the safest way for me to increase the dose of 4-AP beyond 10 mg every six hours. If you are getting benefits from an ... How long should I take 4-AP before I know that it is effective or not? The effects of 4-AP should be apparent within an hour ...
more infohttp://sci.rutgers.edu/forum/showthread.php?20858-4-Aminopyridine-treatment-for-chronic-spinal-cord-injury&s=d5eb91b214bee30dceec0a27318ecaef
4-Aminopyridine in Episodic Ataxia Type 2 - Full Text View - ClinicalTrials.gov  4-Aminopyridine in Episodic Ataxia Type 2 - Full Text View - ClinicalTrials.gov
2004 Mar 4;41(5):701-10. van Diemen HA, Polman CH, van Dongen TM, van Loenen AC, Nauta JJ, Taphoorn MJ, van Walbeek HK, ... 4-Aminopyridine in Episodic Ataxia Type 2 (4AP in EA2). The recruitment status of this study is unknown. The completion date ... Epub 2009 Dec 4. Spyker DA, Lynch C, Shabanowitz J, Sinn JA. Poisoning with 4-aminopyridine: report of three cases. Clin ... 1980 Jun;16(4):487-97. Stefoski D, Davis FA, Faut M, Schauf CL. 4-Aminopyridine improves clinical signs in multiple sclerosis. ...
more infohttps://clinicaltrials.gov/ct2/show/NCT01543750?term=Ataxia&rank=2
4-aminopyridine and cerebellar gait: a retrospective case series. | Sigma-Aldrich  4-aminopyridine and cerebellar gait: a retrospective case series. | Sigma-Aldrich
4-aminopyridine and cerebellar gait: a retrospective case series.. [Roman Schniepp, Max Wuehr, Maximilian Neuhaeusser, Ann ...
more infohttps://www.sigmaaldrich.com/catalog/papers/22760944
Characterizing Concentration-Dependent Neural Dynamics of 4-Aminopyridine-Induced Epileptiform Activity  Characterizing Concentration-Dependent Neural Dynamics of 4-Aminopyridine-Induced Epileptiform Activity
... aminopyridine (4AP) is strongly concentration-dependent. Different 4AP concentrations are characterized by qualitatively ... Timothy L Myers1,2, Oscar C Gonzalez3,4, Jacob B Stein2 and Maxim Bazhenov3*. 1Neuroscience Graduate Program, University of ... Epilepsy J 4:128. DOI: 10.4172/2472-0895.1000128 Copyright: © 2018 Myers TL, et al. This is an open-access article distributed ... 4Neuroscience Graduate Program, University of California, San Diego, California, United States of America. *Corresponding ...
more infohttps://www.omicsonline.org/open-access/characterizing-concentrationdependent-neural-dynamics-of-4aminopyridineinduced-epileptiform-activity-2472-0895-1000128-102706.html
4-Aminopyridine SOP | EHS  4-Aminopyridine SOP | EHS
2018 UW Environmental Health & Safety Department , 201 Hall Health Center, Box 354400, Seattle, WA , Tel: 206.543.7262 , Fax: 206.543.3351 , [email protected] ...
more infohttp://www.ehs.washington.edu/resource/4-aminopyridine-sop-675
Europe 4 Aminopyridine Market Report 2017 - Absolute Reports  Europe 4 Aminopyridine Market Report 2017 - Absolute Reports
Request sample of market research report on Europe 4 Aminopyridine Market Report 2017. Explore detailed TOC, tables and figures ... 5.3 UK 4-Aminopyridine Sales and Market Share by Type. 5.4 UK 4-Aminopyridine Sales and Market Share by Application. 6 Russia 4 ... Aminopyridine (Volume, Value and Sales Price). 6.1 Russia 4-Aminopyridine Sales and Value (2012-2017). 6.1.1 Russia 4- ... Aminopyridine Sales and Growth Rate (2012-2017). 6.1.2 Russia 4-Aminopyridine Revenue and Growth Rate (2012-2017). 6.1.6 Russia ...
more infohttps://www.absolutereports.com/europe-4-aminopyridine-market-report-2017-10615658
4-Aminopyridine (Avitrol) - Chemical Profile 1/85  4-Aminopyridine (Avitrol) - Chemical Profile 1/85
... 4-aminopyridine CHEMICAL name: 4-aminopyridine TRADE name(S): Avitrol (56) ... Pancuronium is an antagonist of 4-aminopyridine, and can control seizures. It must be administered under the supervision of an ... 3.8-4 mg/kg starlings 5-6 mg/kg pigeons 4-7 mg/kg blackbirds 9 mg/kg boat-tailed grackle 3.2 mg/kg (72a) The secondary ...
more infohttp://pmep.cce.cornell.edu/profiles/rodent/rodent_A_L/4-aminopyridine/aminopyr_prf_0185.html
Cholinergic mechanisms in heart: interactions with 4-aminopyridine. | Journal of Pharmacology and Experimental Therapeutics  Cholinergic mechanisms in heart: interactions with 4-aminopyridine. | Journal of Pharmacology and Experimental Therapeutics
Cholinergic mechanisms in heart: interactions with 4-aminopyridine. Message Subject (Your Name) has forwarded a page to you ... 4-Aminopyridine lengthened the action potential and increased spike amplitude. These effects were not frequency-dependent but ...
more infohttp://jpet.aspetjournals.org/content/210/1/7
JCI -
Leptin inhibits 4-aminopyridine- and pentylenetetrazole-induced seizures and AMPAR-mediated synaptic transmission in...  JCI - Leptin inhibits 4-aminopyridine- and pentylenetetrazole-induced seizures and AMPAR-mediated synaptic transmission in...
Leptin inhibits 4-aminopyridine- and pentylenetetrazole-induced seizures and AMPAR-mediated synaptic transmission in rodents. ... Leptin inhibits 4-aminopyridine- and pentylenetetrazole-induced seizures and AMPAR-mediated synaptic transmission in rodents. ... Focal seizures in rats were induced by neocortical injections of 4-aminopyridine, an inhibitor of voltage-gated K+ channels. ... Leptin inhibited α-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) receptor-mediated synaptic transmission in mouse ...
more infohttps://www.jci.org/articles/view/33009/figure/2
JCI -
Leptin inhibits 4-aminopyridine- and pentylenetetrazole-induced seizures and AMPAR-mediated synaptic transmission in...  JCI - Leptin inhibits 4-aminopyridine- and pentylenetetrazole-induced seizures and AMPAR-mediated synaptic transmission in...
Leptin inhibits 4-aminopyridine- and pentylenetetrazole-induced seizures and AMPAR-mediated synaptic transmission in rodents. ... Leptin inhibits 4-aminopyridine- and pentylenetetrazole-induced seizures and AMPAR-mediated synaptic transmission in rodents. ... Focal seizures in rats were induced by neocortical injections of 4-aminopyridine, an inhibitor of voltage-gated K+ channels. ... Leptin inhibited α-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) receptor-mediated synaptic transmission in mouse ...
more infohttps://www.jci.org/articles/view/33009/figure/6
Beyond Pesticides Daily News Blog  4-aminopyridine Archives - Beyond Pesticides Daily News Blog  Beyond Pesticides Daily News Blog 4-aminopyridine Archives - Beyond Pesticides Daily News Blog
One of the most prominent avicides, Avitrol -the trade name for 4-aminopyridine-i s available as grain baits or powder ... A similar event happened in Schenectady New York in 2006, when Rentokill, Inc., a local exterminator applied 4-aminopyridine in ... stuffed with 4-aminopyridine laced corn was the culprit. The chemical was set out on the roof of a building in effort to ward ...
more infohttps://beyondpesticides.org/dailynewsblog/category/chemicals/4-aminopyridine/
Effect of 4-aminopyridine on nerve terminal action potentials. | Journal of Pharmacology and Experimental Therapeutics  Effect of 4-aminopyridine on nerve terminal action potentials. | Journal of Pharmacology and Experimental Therapeutics
Effect of 4-aminopyridine on nerve terminal action potentials. Message Subject (Your Name) has forwarded a page to you from ... Effect of 4-aminopyridine on nerve terminal action potentials.. E S Burley and R S Jacobs ... Effect of 4-aminopyridine on nerve terminal action potentials.. E S Burley and R S Jacobs ... Effect of 4-aminopyridine on nerve terminal action potentials.. E S Burley and R S Jacobs ...
more infohttp://jpet.aspetjournals.org/content/219/1/268
4-Aminopyridine-2,6-Dicarboxylic Acid (CAS 2683-49-0) Market Research Report 2018  4-Aminopyridine-2,6-Dicarboxylic Acid (CAS 2683-49-0) Market Research Report 2018
... aims at providing comprehensive data on 4- ... 4-Aminopyridine-2,6-Dicarboxylic Acid (CAS 2683-49-0) Market Research Report 2018. Date:. January 15, 2018 ... 4-aminopyridine-2,6-dicarboxylic acid prices in other regions. 7. 4-AMINOPYRIDINE-2,6-DICARBOXYLIC ACID END-USE SECTOR 7.1. 4- ... aminopyridine-2,6-dicarboxylic acid market by application sphere. 7.2. 4-aminopyridine-2,6-dicarboxylic acid downstream markets ...
more infohttps://marketpublishers.com/report/industry/chemicals_petrochemicals/cbindex_2683-49-0_market_research_report.html
  • Aminopyridines and Similarly Acting Drugs: Effects on Nerves, Muscles and Synapses presents the proceedings of a IUPHAR Satellite Symposium in conjunction with the eighth International Congress of Pharmacology held in Paris, France on July 27-29, 1981. (elsevier.com)
  • The Effect of 3-, 4-AP and 3,4-DAP on the Evoked Activity of the Pyramidal Cell Layer (CA 1,2) of the Hippocampus. (elsevier.com)
  • 4-AP inhibits basal and FSH-stimulated progesterone production by pig granulosa cells via drug action at multiple interacting steps in the steroidogenic pathway. (biomedcentral.com)
  • The extracellular parameters evaluated in areas CA3 and CAI were: (1) interictal-type bursting, (2) evoked population spike (PS) amplitude, (3) latency to PS onset, and (4) duration of the excitatory postsynaptic potential (EPSP). (deepdyve.com)
  • Similarly, IA and ID antagonist 4-aminopyridine (4AP) has been shown, in in vivo and in vitro studies, to cause hyperexcitability and the development of seizure-like epileptiform discharges [ 15 - 23 ]. (omicsonline.org)
  • The results show that 4-AP induced changes in vitro can help differentiate drugs with similar in vivo spectrums of anticonvulsant activity. (deepdyve.com)
  • Although we could not isolate strain 4AP-Y on several media, PCR-DGGE analysis and microscopy indicated that the unique bi-polar filamentous bacterial cells gradually became more dominant with increasing 4-aminopyridine concentration in the medium. (biomedcentral.com)
  • Leptin inhibited α-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) receptor-mediated synaptic transmission in mouse hippocampal slices but failed to inhibit synaptic responses in slices from leptin receptor-deficient db/db mice. (jci.org)
  • PHT and CBZ partially reversed the increase in EPSP duration produced by 4-AP in area CA3, while the spontaneous bursting was not affected. (deepdyve.com)
  • LOS partially reversed the 4-AP excitation, but abolished bursting in only one of five slices. (deepdyve.com)
  • It also partially reversed the 4-AP induced increase in the EPSP duration without depressing the normal evoked potential. (deepdyve.com)
  • The study participant will be interviewed by phone regarding toxicity using the [Common Terminology Criteria for Adverse Events (CTCAE) Version 4.at two different time points (4 weeks, 8 weeks) of each 8-week Treatment Period. (clinicaltrials.gov)
  • In contrast, Kv1.2 channels displayed a shift in voltage dependence of activation, and this characteristic was also evident during 4-AP treatment when Kv1.2 was coexpressed with Kv1.5 or coupled to Kv1.5 in a tandem construct to produce heterotetrameric [Kv1.5/Kv1.2 channels. (ahajournals.org)
  • In addition, an experimental drug, 4-aminopyridine , appears to increase the velocity of impulses in demyelinated nerves. (thefreedictionary.com)
  • They will receive ascending doses of the drug starting with 10 milligrams and progressively increasing every 2 to 4 weeks 10 mg until reaching the maximum dose proposed according to weight (maximum 1 mg/kg/d). (clinicaltrials.gov)
  • The findings of this study (1) indicate that vascular K DR are inhibited by 4-AP via an open-state block mechanism and trapping of the drug within the pore on channel closure and (2) provide novel evidence based on a comparison of functional characteristics that indicate the dominant form of vascular K DR channel complex in RPV involves the heteromultimeric association of Kv1.2 and Kv1.5 subunits. (ahajournals.org)
  • RPV K DR were found to be inhibited by 4-AP while in the open state, but the drug remains trapped in the pore during channel closure. (ahajournals.org)
  • 4-Aminopyridine is a potent convulsant and is used to generate seizures in animal models for the evaluation of antiseizure agents. (wikipedia.org)
  • Due to the fact that no commercial preparation for 4-AP is available in Belgium, the medication must be compounded by the pharmacist upon medical prescription. (hindawi.com)
  • This study aims to determine whether 4-aminopyridine (4AP) can reduce attacks of ataxia in patients with episodic ataxia type 2 (EA2), a rare but often debilitating condition. (clinicaltrials.gov)
  • In contrast, high concentrations (5 X 10(-4) M) of 4AP prolonged the duration of the NTAP by selectively flattening the K+ slope of the NTAP and increased the quantal content of the end-plate potential. (aspetjournals.org)
  • Inhibition by 4-aminopyridine (4-AP) of K DR of rabbit portal vein (RPV) myocytes was studied by patch clamp and compared with that of channels composed of Kv1.5 and/or Kv1.2 subunits cloned from the RPV and expressed in mammalian cells. (ahajournals.org)
  • DIDS also prevented 4-AP inhibition of progesterone production. (biomedcentral.com)
  • A study has shown that 4-AP is a potent calcium channel activator and can improve synaptic and neuromuscular function by directly acting on the calcium channel beta subunit. (wikipedia.org)
  • 4-AP block of K DR was pulse-frequency dependent, required channel activation, and was associated with a positive shift in voltage dependence of activation. (ahajournals.org)
  • 4-AP caused a voltage-dependent reduction in mean open time of K DR . Relief of 4-AP block of whole cell currents during washout required channel activation and was unaffected by voltage. (ahajournals.org)
  • All Phe-for-heptad-Leu substitutions produce gating changes suggesting variable stabilization of the channel closed state conformation, with L1F, L2F, and L5F exhibiting the strongest correlations between altered gating and increased 4-AP sensitivity. (aspetjournals.org)
  • The dose of 4-aminopyridine will increase 10 mg / every 2 to 4 weeks until reaching the maximum dose proposed by weight ( maximum 1 mg / kg / d). (clinicaltrials.gov)
  • L1F (L457) and L3F (L471) increase 4-AP sensitivity by 8- and 150-fold, respectively, and produce depolarizing shifts in activation of ∼5 mV without affecting inactivation. (aspetjournals.org)
  • Changes in the bacterial populations of 4-aminopyridine, 3,4-dihydroxypyridine, or formate/ammonium chloride enrichment cultures were monitored by denaturing gradient gel electrophoresis (DGGE) profiling of PCR-amplified 16S rRNA gene fragments. (biomedcentral.com)
  • 4AP-Z were predominant in 4-aminopyridine and formate/ammonium chloride enrichment cultures and in the 3,4-dihydroxypyridine enrichment culture, respectively. (biomedcentral.com)
  • 4-AP (2 mM) decreased progesterone accumulation in the media of serum-supplemented and serum-free granulosa cultures, but inhibited cell proliferation only under serum-free conditions. (biomedcentral.com)
  • 1 For example, 4-AP was used to indicate the participation of delayed rectifier K + channels (K DR ) in regulating membrane potential, endothelium-dependent relaxation, and myogenic tone development of VSM (eg, Leblanc et al, 2 Knot and Nelson, 3 and Dong et al 4 ). (ahajournals.org)
  • The results indicated that 4-AP is a potent reversal agent for sedation caused by xylazine in goats. (ac.ke)
  • At the present, 4-AP comes from compounding pharmacies in two formulations. (rutgers.edu)
  • 10-12 Previous studies show considerable variability in the state-dependence of 4-AP block, eg, during or after activation (open-state block), closed (resting)-state block, or block after inactivation. (ahajournals.org)
  • if the dose was sub-lethal, the birds will recover after 4 or more hours without long-term ill effect. (wikipedia.org)
  • We report a case of sustained encephalopathy following status epilepticus induced by 4-AP overdose. (hindawi.com)