Epilepsies, Myoclonic: A clinically diverse group of epilepsy syndromes characterized either by myoclonic seizures or by myoclonus in association with other seizure types. Myoclonic epilepsy syndromes are divided into three subtypes based on etiology: familial, cryptogenic, and symptomatic (i.e., occurring secondary to known disease processes such as infections, hypoxic-ischemic injuries, trauma, etc.).NAV1.1 Voltage-Gated Sodium Channel: A voltage-gated sodium channel subtype that is predominantly expressed in the CENTRAL NERVOUS SYSTEM. Defects in the SCN1A gene which codes for the alpha subunit of this sodium channel are associated with DRAVET SYNDROME, generalized epilepsy with febrile seizures plus, type 2 (GEFS+2), and familial hemiplegic migraine type 3.Myoclonic Epilepsy, Juvenile: A disorder characterized by the onset of myoclonus in adolescence, a marked increase in the incidence of absence seizures (see EPILEPSY, ABSENCE), and generalized major motor seizures (see EPILEPSY, TONIC-CLONIC). The myoclonic episodes tend to occur shortly after awakening. Seizures tend to be aggravated by sleep deprivation and alcohol consumption. Hereditary and sporadic forms have been identified. (From Adams et al., Principles of Neurology, 6th ed, p323)Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Mutation, Missense: A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)Epilepsy, Generalized: Recurrent conditions characterized by epileptic seizures which arise diffusely and simultaneously from both hemispheres of the brain. Classification is generally based upon motor manifestations of the seizure (e.g., convulsive, nonconvulsive, akinetic, atonic, etc.) or etiology (e.g., idiopathic, cryptogenic, and symptomatic). (From Mayo Clin Proc, 1996 Apr;71(4):405-14)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)Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Seizures, Febrile: Seizures that occur during a febrile episode. It is a common condition, affecting 2-5% of children aged 3 months to five years. An autosomal dominant pattern of inheritance has been identified in some families. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy (i.e., a nonfebrile seizure disorder) following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy. (From Menkes, Textbook of Child Neurology, 5th ed, p784)Sodium Channels: Ion channels that specifically allow the passage of SODIUM ions. A variety of specific sodium channel subtypes are involved in serving specialized functions such as neuronal signaling, CARDIAC MUSCLE contraction, and KIDNEY function.Conotoxins: Peptide neurotoxins from the marine fish-hunting snails of the genus CONUS. They contain 13 to 29 amino acids which are strongly basic and are highly cross-linked by disulfide bonds. There are three types of conotoxins, omega-, alpha-, and mu-. OMEGA-CONOTOXINS inhibit voltage-activated entry of calcium into the presynaptic membrane and therefore the release of ACETYLCHOLINE. Alpha-conotoxins inhibit the postsynaptic acetylcholine receptor. Mu-conotoxins prevent the generation of muscle action potentials. (From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed)Conus Snail: A genus of cone-shaped marine snails in the family Conidae, class GASTROPODA. It comprises more than 600 species, many containing unique venoms (CONUS VENOMS) with which they immobilize their prey.Calcium Channels, N-Type: CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.Mollusk Venoms: Venoms from mollusks, including CONUS and OCTOPUS species. The venoms contain proteins, enzymes, choline derivatives, slow-reacting substances, and several characterized polypeptide toxins that affect the nervous system. Mollusk venoms include cephalotoxin, venerupin, maculotoxin, surugatoxin, conotoxins, and murexine.omega-Conotoxins: A family of structurally related neurotoxic peptides from mollusk venom that inhibit voltage-activated entry of calcium into the presynaptic membrane. They selectively inhibit N-, P-, and Q-type calcium channels.Biological Products: Complex pharmaceutical substances, preparations, or matter derived from organisms usually obtained by biological methods or assay.omega-Conotoxin GVIA: A neurotoxic peptide, which is a cleavage product (VIa) of the omega-Conotoxin precursor protein contained in venom from the marine snail, CONUS geographus. It is an antagonist of CALCIUM CHANNELS, N-TYPE.Snails: Marine, freshwater, or terrestrial mollusks of the class Gastropoda. Most have an enclosing spiral shell, and several genera harbor parasites pathogenic to man.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.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.Hematologic Diseases: Disorders of the blood and blood forming tissues.Pulmonary Disease, Chronic Obstructive: A disease of chronic diffuse irreversible airflow obstruction. Subcategories of COPD include CHRONIC BRONCHITIS and PULMONARY EMPHYSEMA.Sleep Disorders: Conditions characterized by disturbances of usual sleep patterns or behaviors. Sleep disorders may be divided into three major categories: DYSSOMNIAS (i.e. disorders characterized by insomnia or hypersomnia), PARASOMNIAS (abnormal sleep behaviors), and sleep disorders secondary to medical or psychiatric disorders. (From Thorpy, Sleep Disorders Medicine, 1994, p187)Sleep: A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Heart: The hollow, muscular organ that maintains the circulation of the blood.Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level.Lung Diseases, Obstructive: Any disorder marked by obstruction of conducting airways of the lung. AIRWAY OBSTRUCTION may be acute, chronic, intermittent, or persistent.Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.United StatesRisk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.Encyclopedias as Topic: Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)Calcium Channels, L-Type: Long-lasting voltage-gated CALCIUM CHANNELS found in both excitable and nonexcitable tissue. They are responsible for normal myocardial and vascular smooth muscle contractility. Five subunits (alpha-1, alpha-2, beta, gamma, and delta) make up the L-type channel. The alpha-1 subunit is the binding site for calcium-based antagonists. Dihydropyridine-based calcium antagonists are used as markers for these binding sites.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.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.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, Calcium-Activated: Potassium channels whose activation is dependent on intracellular calcium concentrations.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.
N-type voltage-dependent calcium channels mediate the nicotinic enhancement of GABA release in chick brain. (1/34)The role of voltage-dependent calcium channels (VDCCs) in the nicotinic acetylcholine receptor (nAChR)-mediated enhancement of spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) was investigated in chick brain slices. Whole cell recordings of neurons in the lateral spiriform (SpL) and ventral lateral geniculate (LGNv) nuclei showed that cadmium chloride (CdCl2) blocked the carbachol-induced increase of spontaneous GABAergic IPSCs, indicating that VDCCs might be involved. To conclusively show a role for VDCCs, the presynaptic effect of carbachol on SpL and LGNv neurons was examined in the presence of selective blockers of VDCC subtypes. omega-Conotoxin GVIA, a selective antagonist of N-type channels, significantly reduced the nAChR-mediated enhancement of gamma-aminobutyric acid (GABA) release in the SpL by 78% compared with control responses. Nifedipine, an L-type channel blocker, and omega-Agatoxin-TK, a P/Q-type channel blocker, did not inhibit the enhancement of GABAergic IPSCs. In the LGNv, omega-Conotoxin GVIA also significantly reduced the nAChR-mediated enhancement of GABA release by 71% from control values. Although omega-Agatoxin-TK did not block the nicotinic enhancement, L-type channel blockers showed complex effects on the nAChR-mediated enhancement. These results indicate that the nAChR-mediated enhancement of spontaneous GABAergic IPSCs requires activation of N-type channels in both the SpL and LGNv. (+info)
N-Type Ca(2+) channels trigger release of excitatory and inhibitory neurotransmitter from nerve endings in canine bronchi. (2/34)We set out to characterize the types of Ca(2+) channels that mediate release of the predominant excitatory (acetylcholine) and inhibitory (norepinephrine) neurotransmitters in canine bronchi, using electrically evoked contractions and relaxations, respectively, as indicators of this release. We found that the selective N-type Ca(2+) channel blocker (omega-conotoxin GVIA) eliminated electrically evoked contractions in a dose-dependent fashion (half-maximal inhibition in the presence of 1-5 nM) but had no significant effect on those evoked by exogenously added acetylcholine. Selective blockers of P-type Ca(2+) channels (omega-agatoxin TK; 10(-8) to 10(-7) M) or of L-type Ca(2+) channels (nifedipine; 10(-8) to 10(-6) M) had no significant effect on the responses to neurally released or exogenously added acetylcholine. Likewise, electrically evoked relaxations were blocked by omega-conotoxin GVIA (10(-7) M) but not by omega-agatoxin TK (10(-7) M) or nifedipine (10(-7) M); none of these Ca(2+) channel blockers had a significant inhibitory effect on isoproterenol-triggered relaxations. We conclude that excitatory and inhibitory neurotransmission in canine bronchi is mediated predominantly by N-type Ca(2+) channels, with little or no contribution from L-, P-, Q-, or T-type channels. (+info)
Role of glutamate receptors and voltage-dependent calcium channels in glutamate toxicity in energy-compromised cortical neurons. (3/34)We have examined the effect of glutamate receptor antagonists and voltage-dependent calcium channel blockers on the neuronal injury induced by the combination of a low concentration of N-methyl-D-aspartate (NMDA) or kainate and energy compromise resulting from the use of glucose-free incubation buffer. Toxicity induced by NMDA or kainate was enhanced in the glucose-free buffer. NMDA-or non-NMDA-receptor antagonists added to the glucose-free buffer at the same time inhibited the neuronal cell death induced by each agonist. An NMDA-receptor antagonist, MK-801, but not non-NMDA-receptor antagonists, inhibited the toxicity when added to the culture medium after exposure of the cells to the agonists. P/Q-type calcium channel blockers, omega-agatoxin IVA and omega-agatoxin TK, and an N-type calcium channel blocker, omega-conotoxin GVIA, significantly attenuated the neuronal injury, although an L-type calcium channel blocker, nifedipine, showed little neuroprotective effect. A combination of calcium channel blockers of the three subtypes showed the most prominent neuroprotective effect. These observations suggest that the overactivation of NMDA and non-NMDA receptors and consequent activation of the voltage-dependent calcium channels lead to neuronal cell death in energy-compromised cortical neurons. (+info)
The spider toxin omega-Aga IIIA defines a high affinity site on neuronal high voltage-activated calcium channels. (4/34)The spider toxin omega-agatoxin IIIA (omega-Aga-IIIA) is a potent inhibitor of high voltage-activated calcium currents in the mammalian brain. To establish the biochemical parameters governing its action, we radiolabeled the toxin and examined its binding to native and recombinant calcium channels. In experiments with purified rat synaptosomal membranes, both kinetic and equilibrium data demonstrate one-to-one binding of omega-Aga-IIIA to a single population of high affinity sites, with K(d) = approximately 9 pm and B(max) = approximately 1.4 pmol/mg protein. Partial inhibition of omega-Aga-IIIA binding by omega-conotoxins GVIA, MVIIA, and MVIIC identifies N and P/Q channels as components of this population. omega-Aga-IIIA binds to recombinant alpha(1B) and alpha(1E) calcium channels with a similar high affinity (K(d) = approximately 5-9 pm) in apparent one-to-one fashion. Results from recombinant alpha(1B) binding experiments demonstrate virtually identical B(max) values for omega-Aga-IIIA and omega-conotoxin MVIIA, providing further evidence for a one-to-one stoichiometry of agatoxin binding to calcium channels. The combined evidence suggests that omega-Aga-IIIA defines a unique, high affinity binding site on N-, P/Q-, and R-type calcium channels. (+info)
All classes of calcium channel couple with equal efficiency to exocytosis in rat melanotropes, inducing linear stimulus-secretion coupling. (5/34)1. The contribution of low voltage-activated (LVA) T-type Ca2+ channels and four different types of high voltage-activated (HVA) Ca2+ channel to exocytosis, and the relationship between calcium influx and exocytosis during action potentials (APs) were studied in pituitary melanotropes. 2. Selective HVA Ca2+ channel blockers reduced exocytosis, monitored by membrane capacitance measurements, proportional to the reduction in Ca2+ influx. The efficacy of Ca2+ in stimulating exocytosis did not change in the presence of the Ca2+ channel blockers, indicating that all HVA Ca2+ channels act together in stimulating exocytosis. 3. The relationship between Ca2+ influx and exocytosis during the AP was examined using APs recorded from spontaneously active melanotropes as command templates under voltage clamp. Under voltage clamp, multiphasic Ca2+ currents were activated over the entire duration of the APs, i.e. during the rising phase as well as the plateau phase. The maximum amplitude of the Ca2+ current coincided with the peak of the AP. 4. The relationship between Ca2+ entry and exocytosis was linear for the different phases of the AP. Also, the influx of Ca2+ through LVA T-type channels stimulated exocytosis with the same efficacy as through the HVA channels. 5. APs of increasing duration ( approximately 50 to approximately 300 ms) evoked increasing amounts of exocytosis. The number of entering Ca2+ ions and the capacitance change were linearly related to AP duration, resulting in a fixed relationship between Ca2+ entry and exocytosis. 6. The results show that Ca2+ ions, entering a melanotrope, couple with equal strength to exocytosis regardless of the channel type involved. We suggest that the linear relationship between Ca2+ entry and secretion observed under physiological conditions (during APs), results from the equal strength with which LVA and HVA channels in melanotropes couple to exocytosis. This guarantees that secretion takes place over the entire duration of the AP. (+info)
Dendro-somatic distribution of calcium-mediated electrogenesis in purkinje cells from rat cerebellar slice cultures. (6/34)The role of Ca2+ entry in determining the electrical properties of cerebellar Purkinje cell (PC) dendrites and somata was investigated in cerebellar slice cultures. Immunohistofluorescence demonstrated the presence of at least three distinct types of Ca2+ channel proteins in PCs: the alpha1A subunit (P/Q type Ca2+ channel), the alpha1G subunit (T type) and the alpha1E subunit (R type). In PC dendrites, the response started in 66 % of cases with a slow depolarization (50 +/- 15 ms) triggering one or two fast (approximately 1 ms) action potentials (APs). The slow depolarization was identified as a low-threshold non-P/Q Ca2+ AP initiated, most probably, in the dendrites. In 16 % of cases, this response propagated to the soma to elicit an initial burst of fast APs. Somatic recordings revealed three modes of discharge. In mode 1, PCs display a single or a short burst of fast APs. In contrast, PCs fire repetitively in mode 2 and 3, with a sustained discharge of APs in mode 2, and bursts of APs in mode 3. Removal of external Ca2+ or bath applications of a membrane-permeable Ca2+ chelator abolished repetitive firing. Tetraethylammonium (TEA) prolonged dendritic and somatic fast APs by a depolarizing plateau sensitive to Cd2+ and to omega-conotoxin MVII C or omega-agatoxin TK. Therefore, the role of Ca2+ channels in determining somatic PC firing has been investigated. Cd2+ or P/Q type Ca2+ channel-specific toxins reduced the duration of the discharge and occasionallyinduced the appearance of oscillations in the membrane potential associated with bursts of APs. In summary, we demonstrate that Ca2+ entry through low-voltage gated Ca2+ channels, not yet identified, underlies a dendritic AP rarelyeliciting a somatic burst of APs whereas Ca2+ entry through P/Q type Ca2+ channels allowed a repetitive firing mainly by inducing a Ca2+-dependent hyperpolarization. (+info)
Isolation, synthesis and pharmacological characterization of delta-palutoxins IT, novel insecticidal toxins from the spider Paracoelotes luctuosus (Amaurobiidae). (7/34)Four novel insecticidal toxins were isolated from the venom of the spider Paracoelotes luctuosus (Araneae: Amaurobiidae) and named delta-palutoxins IT1 to IT4. The four toxins are homologous 36-37 amino acid peptides reticulated by four disulfide bridges and three have amidated C-terminal residues. The delta-palutoxins are highly homologous with the previously described mu-agatoxins and curtatoxins (77-97%). The four peptides demonstrated significant toxicity against larvae of the crop pest Spodoptera litura (Lepidoptera: Noctuidae) in a microinjection bioassay, with LD50 values in the 9-50 microg per g of insect range. This level of toxicity is equivalent to that of several of the most active scorpion toxins used in the development of recombinant baculoviruses, and the delta-palutoxins appear to be insect specific. Electrophysiological experiments demonstrated that delta-palutoxin IT1, the most active toxin acts by affecting insect sodium channel inactivation, resulting in the appearance of a late-maintained sodium current, in a similar fashion to insecticidal scorpion alpha and alpha-like toxins and is thus likely to bind to channel receptor site 3. However, delta-palutoxin IT1 was distinguished by its lack of effect on peak sodium conductance, on the early phase of sodium current inactivation and the absence of a shift in the activation voltage of the sodium channels. delta-Palutoxins are thus proposed as new insecticidal toxins related to the alpha and alpha-like scorpion toxins. They will be useful both in the development of recombinant baculoviruses in agrochemical applications and also as molecular probes for the investigation of molecular mechanisms of insect selectivity and structure and function of sodium channels. (+info)
Oxytocin retrogradely inhibits evoked, but not miniature, EPSCs in the rat supraoptic nucleus: role of N- and P/Q-type calcium channels. (8/34)We previously reported that oxytocin (OXT), released from the dendrites of magnocellular neurons in the supraoptic nucleus (SON), acts retrogradely on presynaptic terminals to inhibit glutamatergic transmission. Here we test the hypothesis that oxytocin reduces calcium influx into the presynaptic terminal. We used nystatin perforated-patch recording in vitro to first identify the calcium channels involved in glutamatergic transmission in the SON. [omega]-Conotoxin GVIA ([omega]-CTx) and [omega]-Agatoxin TK ([omega]-Aga) both reduced evoked EPSC amplitude, while nicardipine and nickel had no effect. A combination of [omega]-CTx and [omega]-Aga completely abolished the evoked EPSCs. This depressant effect was accompanied by an increase in the paired pulse ratio with no change in the kinetics of the evoked EPSCs, AMPA currents or postsynaptic cell properties. These results suggest that presynaptic N- and P/Q-type calcium channels mediate glutamate release in the SON while L-, T- and R-type channels make little or no contribution. Oxytocin-induced reduction of the evoked EPSC was substantially occluded in the presence of [omega]-CTx but only partially in the presence of [omega]-Aga. Amastatin, an endopeptidase inhibitor that increases the level of endogenous OXT, also reduced the evoked EPSC. This amastatin effect was also occluded by [omega]-CTx and [omega]-Aga. Miniature EPSCs, which are independent of extracellular calcium, were unaffected by either [omega]-CTx or by OXT, thus further substantiating an action of both compounds on calcium channels. Therefore, dendritically released oxytocin acts mainly via a mechanism involving the N-type channel, and to a lesser extent the P/Q-type channel, to decrease excitatory transmission. (+info)
Voltage-gated calcium channel
... the closely related P/Q-type channel blocked by ω-agatoxins, and the dihydropyridine-sensitive L-type channels responsible for ...
... belongs to toxin group of Agatoxins. The amino acid structure of agelenin is Gly-Gly-Cys-Leu-Pro-His-Asn-Arg-Phe-Cys- ...
... aperta, the American funnel-web spider, produces agatoxins. Their bite causes rapid paralysis in insect prey, ...
"Structure-activity relationships for P-type calcium channel-selective omega-agatoxins". Nat. Struct. Biol. 1 (12): 853-6. doi: ...
The disulfide bonding pattern found in δ-Palutoxins is very similar to the pattern seen in µ-Agatoxins. This indicates strong ... homologies with the µ-Agatoxins from Agelenopsis aperta. Voltage-gated sodium channels have neurotoxin binding sites on their α ...
Agatoxins may be divided into three major structural subclasses: Alpha-agatoxins are composed of polyamines which are attached ... Agatoxins are a class of chemically diverse polyamine and peptide toxins which are isolated from the venom of various spiders. ... In several of the omega-agatoxins contain one or more D-amino acids which are produced from L-amino acids through the action of ... Omega-agatoxins in turn are subdivided in four classes based on their primary structures, biochemical properties and calcium ...
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My work is at the interface between behavior, ecology and evolutionary biology with a central focus on the extent to which populations are at adaptive equilibria with respect to their physical and biotic environments. These questions are pursued through genetic analyses of fitness-linked traits, through species optimum and game theoretic analyses and simulations, and through field manipulations and breeding experiments. Current work on the desert spider, Agelenopsis aperta, involves a quantitative genetic study of the effect of competitive interactions among conspecifics on the joint evolution of aggressiveness and body size. Aggressiveness is a social trait that is both a characteristic of an individual and of the environment. The results of a breeding experiment presented in Riechert and Johns (2005) suggested that while such factors as metabolic rate and assimilation efficiency are heritable, their effects on an individuals phenotype are overridden by behavioral aggressiveness which also is ...
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Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the high-voltage activated (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1C subunit play an important role in excitation-contraction coupling in the heart. The various isoforms display marked differences in the sensitivity to DHP compounds. Binding of calmodulin or CABP1 at the same regulatory sites results in an opposit effects on the channel function ...
0000-0002-2557-6204 Today, PLOS Biology blazes a new trail for PLOS; were the first journal to go live on PLOS new manuscript submission system, Aperta™. Aperta offers a refreshing look and feel, with a unique and clean. ...
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A new peptide antagonist of voltage-activated calcium channels was purified from venom of the funnel web spider, Agelenopsis aperta. This 48-amino acid peptide, omega-agatoxin (omega-Aga)-IVB, was found to be a potent (Kd, approximately 3 nM) blocker of P-type calcium channels in rat cerebellar Purkinje neurons but had no activity against T-type, L-type, or N-type calcium channels in a variety of neurons. The calcium channel-blocking properties of omega-Aga-IVB were similar to those of another toxin, omega-Aga-IVA, which has 71% amino acid identity with omega-Aga-IVB. The 10-fold greater abundance of omega-Aga-IVB in venom allowed structural studies using NMR spectroscopy. The three-dimensional structure derived from NMR data resulted in a proposed disulfide bond configuration for the peptide. Although omega-Aga-IVB has fewer basic and more acidic residues than does omega-Aga-IVA, the two toxins show conservation of positively charged residues in a mid-peptide region that is predicted to form ...
A reconfiguration of Ca(V)2Ca(2+) channel current and its dopaminergic D-2 modulation in developing neostriatal neurons
The modulatory effect of D 2 dopamine receptor activation on calcium currents was studied in neostriatal projection neurons at two stages of rat development: postnatal day (PD)14 and PD40. D-2-class receptor agonists reduced whole cell calcium currents by about 35% at both stages, and this effect was blocked by the D-2 receptor antagonist sulpiride. Nitrendipine partially occluded this modulation at both stages, indicating that modulation of Ca(V)1 channels was present throughout this developmental interval. Nevertheless, modulation of Ca(V)1 channels was significantly larger in PD40 neurons. omega-Conotoxin GVIA occluded most of the Ca2+ current modulation in PD14 neurons. However, this occlusion was greatly decreased in PD40 neurons. omega-Agatoxin TK occluded a great part of the modulation in PD40 neurons but had a negligible effect in PD14 neurons. The data indicate that dopaminergic D-2-mediated modulation undergoes a change in target during development: from Ca(V)2.2 to Ca(V)2.1 Ca2+ ...
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1F gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the high-voltage activated (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA ...
Ingredient in funnel web spider venom can protect cells from being destroyed by a stroke, even when given hours after the event, study shows The protective molecule was discovered by chance as researchers sequenced the DNA of toxins in the venom of Hadronyche infensa, the Darling Downs funnel web spider. Doctors have stumbled on an…
Different types of Ca2+ channels have been identified in neuronal soma. P-type Ca2+ channels resistant to the blocking effect of dihydropyridines and w-conotoxin-GVIA but sensitive to the funnel web spider toxin and w-agatoxin-IVA mediate the influx of Ca2+ involved in transmitter release in mammalian synapses.. ...
A bite from an Australian funnel web spider can kill a human in 15 minutes - but its venom could prove to be the worlds first treatment for brain damage caused by a stroke. Scientists were sequencing the DNA of the venom when they stumbled upon a compound, which they believe may have wide- ...
Cacna1c - Voltage-dependent L-type calcium channel subunit alpha - Mus musculus (Mouse) - Cacna1c gene & protein
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the high-voltage activated (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1C subunit play an important role in excitation-contraction coupling in the heart. Binding of calmodulin or CABP1 at the same regulatory sites results in an opposit effects on the channel function.
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1S gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the high-voltage activated (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle ...
Australian funnel-web spiders (family Hexathelidae, subfamily Atracinae, genera Atrax and Hadronyche) are among the most venomous spiders in the world based on clinical experience in Australia, although their importance to human health is limited by their confined geographic range. Funnel-web spiders belong to the suborder Mygalomorphae, a pr...
New engineered spider protein could be the start of a new generation of anti-venom vaccines, potentially saving thousands of lives worldwide. The new protein, created from parts of a toxin from the reaper spider, is described today in the Elsevier journal Vaccine.
[email protected] staff is a group of interracial international politically charged women who are educated in the fields of community studies, creative writing, critical dance theory and performance management, feminist studies, Latin American studies and sociology. They most sincerely love the various and extensive roles they play within the department and its community ...
Spiders at Spiderzrule - the best site in the world about spiders, redbacks, huntsmen, garden orb weaver, funnel web, black...
spiders, redbacks, huntsmen, garden orb weaver, funnel web, black widow, recluse, hobo spider, daddy long legs, venom, bites, webs, hoaxes, spider photos, spider identification
Harry Thurston Peck, Harpers Dictionary of Classical Antiquities (1898), A, Aperta Navis, Apollināris, Sulpicius
Current location in this text. Enter a Perseus citation to go to another section or work. Full search options are on the right side and top of the page ...
Il mondo dei profumi è già affascinante di per sé. Ma quando scopri tutto il lavoro che cè dietro per creare una fragranza, allora resti a bocca aperta. Quando MyFashionMagazine è[...] ...
Cose che non possono passare inosservate: il doodle di oggi - uno dei più semplici e modesti mai visti - è per il 14° compleanno di Google. Auguri a quello che più che un semplice motore di ricerca è una porta aperta dentro le nostre teste. Divertente la schermata qui sopra: nel 1997-98 Google era appena nato, era ancora ospite della Stanford University, usava il punto esclamativo in fondo copiando chiaramente Yahoo!, mandava una newsletter mensile (lol). E soprattutto aveva 25 milioni di pagine indicizzate e prometteva, a proposito del suo indice: "Soon to be much bigger". Fatto: nel 2008 il Google Blog ufficiale annunciava di aver superato "1 trillion (as in 1,000,000,000,000) unique URLs".. ...
Cacna1e - Voltage-dependent R-type calcium channel subunit alpha-1E - Mus musculus (Mouse) - Cacna1e gene & protein
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1E gives rise to R-type calcium currents. R-type calcium channels belong to the high-voltage activated (HVA) group and are blocked by nickel, and partially by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to dihydropyridines (DHP), omega-conotoxin-GVIA (omega-CTx-GVIA), and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing alpha-1E subunit could be involved in the modulation of firing patterns of neurons which is important for information processing.
Also called funnel web spiders, hobo spiders can be aggressive, though they infrequently attack humans unless provoked. The bite of a hobo spider can be very painful and the venom may result in necrosis of the surrounding tissue. Many reported cases of brown recluse bites are, in actuality, hobo spider bites. In cases where a bite results in necrosis, the severity is typically less than that associated with the bite of a brown recluse though the wound may take several weeks or months to heal. The hobo spider is typically found in the northwest region of the country though it is said to have originated from Europe.. ...
One of the most venomous creatures in the Australia outback, the Sydney Funnel Web Spider packs a powerful punch. This spider is large and very aggressive, consistently creating the most powerful venom of any spider. Protecting its burrow, the spider places a web across its entrance that passers by should not enter. From its fangs, the spider delivers a powerful neurotoxin that cause extreme pain and are capable of killing a person within 15 minutes. Its venom does not affect most mammals but has a very powerful effect on humans. ...
Shop Voltage-dependent P/Q-type calcium channel ELISA Kit, Recombinant Protein and Voltage-dependent P/Q-type calcium channel Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.
A new generation of environmentally safe insecticides that only target disease-carrying insects or those that damage crops is emerging from surprising research into the venom of one of the worlds deadliest creatures - the Australian Blue Mountains funnel-web spider.. The spiders potentially fatal effect on humans is an unlucky side-effect of just one of the 200 or so compounds its venom contains. But Dr Glenn King, professor of Biochemistry and Microbiology at the University of Connecticut Health Centre in the U.S. has said that many of the other compounds kill particular insects and are otherwise harmless.. This means the spiders venom has great potential to be developed as insecticides and could be used in two ways; as conventional sprayed pesticides, or delivered by insect-specific viruses that have been genetically engineered to contain a spider-venom gene.. "The latter approach is actually better from an environmental point of view because it is like a magic bullet that targets a ...
Hirsch funnels collect solids from a liquid sample. They resemble Büchner funnels because they use a perforated disk, but they have angled sides and hold a smaller quantity of...
A toxin synthesized from the venom of a spider may offer an alternative to todays erectile dysfunction drugs, a new study suggests.
Fisherbrand™ Heavy-Duty/Utility Funnels Top dia. x H: 155 x 177mm; Capacity: 410mL Fisherbrand™ Heavy-Duty/Utility Funnels
Fisherbrand™ Heavy-Duty/Utility Funnels Top dia. x H: 155 x 177mm; Capacity: 410mL Fisherbrand™ Heavy-Duty/Utility Funnels Plastic Filling Funnels
1994) Calcium channel diversity and neurotransmitter release: the omega-conotoxins and omega-agatoxins. Annu Rev Biochem 63:823 ...http://www.jneurosci.org/content/28/46/11768
Department of Entomology: Faculty
omega-Agatoxins: Novel calcium channel antagonists of two subtypes from funnel web spider (Agelenopsis aperta) venom. J. Biol. ... Adams, M.E. (2004) Agatoxins. Toxicon 43: 509-525. Kim, Y., Spalovska-Valachova, I., Cho, K., Zitnanova, I., Park, Y., Adams, M ... 1992 Antagonism of synaptosomal calcium channels by subtypes of omega-agatoxins. J. Biol. Chem. 267:2610-2615. Mintz, I.M., V.J ... Calcium channel diversity and neurotransmitter release: The w-conotoxins and w-agatoxins. Ann. Rev. Biochem. 63:823-867. Adams ...http://www.entomology.ucr.edu/faculty/adams.html
Calcium Channel Diversity at the Vertebrate Neuromuscular Junction | Springer for Research & Development
... the omega-conotoxins and omega-agatoxins. Annu. Rev. Biochem. 63: 823-67.PubMedCrossRefGoogle Scholar ...https://rd.springer.com/chapter/10.1007/978-1-4757-9555-4_4
Marine Drugs | Free Full-Text | ω-Conotoxins GVIA, MVIIA and CVID: SAR and Clinical Potential | HTML
The ω-Conotoxins and the ω-Agatoxins. Ann. Rev. Biochem 1994, 63, 823-867. [Google Scholar] ...http://www.mdpi.com/1660-3397/4/3/193/htm
Methods for the inhibition of egg production in trematodes - Patent # 6514963 - PatentGenius
The w-agatoxins, also isolated from the funnel web spider, comprise four subtypes. Most of these toxins block only N channels ( ...http://www.patentgenius.com/patent/6514963.html
Agelenin - Wikipedia
Agelenin belongs to toxin group of Agatoxins. The amino acid structure of agelenin is Gly-Gly-Cys-Leu-Pro-His-Asn-Arg-Phe-Cys- ...https://en.wikipedia.org/wiki/Agelenin
Elucidating Nature's Solutions to Heart, Lung, and Blood Diseases and Sleep Disorders | Circulation Research
Agatoxins: Ion channel specific toxins from the American funnel web spider, Agelenopsis aperta. Toxicon. 2004; 43: 509-525. ...http://circres.ahajournals.org/content/110/7/915.full
Agelenopsis - Wikipedia
Agelenopsis aperta, the American funnel-web spider, produces agatoxins. Their bite causes rapid paralysis in insect prey, ...https://en.wikipedia.org/wiki/Agelenopsis
Fingerprint Fingerprint is based on mining the text of the experts scientific documents to create an index of weighted terms, which defines the key subjects of each individual researcher. ...https://miami.pure.elsevier.com/en/persons/john-barrett
Action of Naturally Occurring Toxins and Medicines
Agatoxins are a polyamine and peptide toxins which differ from each other chemically. They are obtained from the venom of ... The agatoxins can be further divided into 3 subclasses, namely, alpha-agatoxin, omega-agatoxin and Mu-agatoxin. Alpha-agatoxin ...https://www.ukessays.com/essays/biology/action-naturally-occurring-toxins-6449.php
CALCIUM AND ENDOCYTOTIC MEMBRANE RETRIEVAL - Augusta University Research Profiles
DESCRIPTION: Endocytotic membrane retrieval compensates for excess surface membrane following exocytosis but the mechanism of exocytosis-endocytosis coupling is not known. We have shown in sea urchin eggs that membrane retrieval requires calcium influx through agatoxin sensitive channels. Thus, in addition to their role in signaling for exocytosis at synapses, P-type calcium channels are required for endocytotic membrane retrieval in eggs. We hypothesize that exocytosis regulates P-type calcium channel gating to coordinate exocytosis and endocytotic membrane retrieval. We will use microscopy, electrophysiology, as well as cell and molecular biological techniques to determine how exocytotic activity regulates calcium influx through P-type channels in sea urchin eggs, a model system for understanding calcium-triggered exocytosis and endocytosis. Specifically we will determine how exocytotic activity influences membrane depolarization and the cellular distribution of P-type calcium channels ...https://augusta.pure.elsevier.com/en/projects/calcium-and-endocytotic-membrane-retrieval
Voltage-gated calcium channel - Wikipedia
... the closely related P/Q-type channel blocked by ω-agatoxins, and the dihydropyridine-sensitive L-type channels responsible for ...https://en.wikipedia.org/wiki/Voltage-gated_calcium_channel
Voltage-gated calcium channel - Wikipedia
... the closely related P/Q-type channel blocked by ω-agatoxins, and the dihydropyridine-sensitive L-type channels responsible for ...https://en.wikipedia.org/wiki/Voltage-dependent_calcium_channel
How Does a Brain Cell Work | Science Features | Naked Scientists
Spiders: agatoxins - which block calcium channels and atracotoxins which cause uncontrollable opening of sodium channels are ...https://www.thenakedscientists.com/articles/science-features/how-does-brain-cell-work
Voltage-dependent calcium channel - The Full Wiki
Characterization of the +SSTR and ΔSSTR splice variants of the Cav2.1 P/Q-type voltage-gated calcium channel - UBC Library Open...
2004) Agatoxins: ion channel specific toxins from the american funnel web spider, Agelenopsis aperta. Toxicon. 43: 509-525. ...https://open.library.ubc.ca/cIRcle/collections/ubctheses/24/items/1.0165825
... after which agatoxins are named. mu-Agatoxins are C-terminally amidated peptides that consist of 35-37 amino acids and are ... Agatoxins are a class of chemically diverse polyamine and peptide toxins which are isolated from the venom of various spiders, ... Agatoxins are a class of chemically diverse polyamine and peptide toxins which are isolated from the venom of various spiders, ... mu-Agatoxins modify presynaptic voltage-activated sodium channels in the neuromuscular joints of insects. Modifying sodium ...http://www.t3db.ca/toxins/T3D2627
Systemic effects induced by intralesional injection of ω-conotoxin MVIIC after spinal cord injury in rats | Journal of Venomous...
... the omega-conotoxins and omega-agatoxins. Annu Rev Biochem 1994, 63: 823-867. 10.1146/annurev.bi.63.070194.004135PubMedGoogle ...https://jvat.biomedcentral.com/articles/10.1186/1678-9199-20-15
Search Articles | University of Toronto Libraries
Agatoxins , Conotoxins - pharmacology , Receptor, Cannabinoid, CB1 - metabolism , Glycerides - pharmacology , Polyamines - ...https://query.library.utoronto.ca/index.php/search/q?kw=SubjectTerms:gamma-Aminobutyric%20Acid%20-%20pharmacology
Cohen, C. J.
Ertel, E. A., Warren, V. A., Adams, M. E., Griffin, P. R., Cohen, C. J., Smith, M. M. Type-III omega-agatoxins - a family of ...https://vivo.scripps.edu/display/endnote376550
Protein Data Bank Japan
Three-dimensional structure analysis of mu-agatoxins: further evidence for common motifs among neurotoxins with diverse ion ... Structure-activity relationships for P-type calcium channel-selective omega-agatoxins.. Nat.Struct.Biol., 1, 1994. ...https://pdbj.org/authorSearch?query=%22+Thanabal%2C+V.%22&sortBy=8
Arthropod Proteins | Profiles RNS
Das S, Vraspir L, Zhou W, Durica DS, Mykles DL. Transcriptomic analysis of differentially expressed genes in the molting gland (Y-organ) of the blackback land crab, Gecarcinus lateralis, during molt-cycle stage transitions. Comp Biochem Physiol Part D Genomics Proteomics. 2018 12; 28:37-53 ...http://profiles.ouhsc.edu/display/71240
omega-Agatoxin IVA | Profiles RNS
Agatoxins [D20.888.065.870.324]. *omega-Agatoxin IVA [D20.888.065.870.324.500]. *Biological Factors [D23] ...https://profiles.umassmed.edu/display/127376
1iva - Summary - PDBj Mine PDB Explorer
... structure-activity relationships for p-type calcium channel selective omega-agatoxins ... Structure-activity relationships for P-type calcium channel-selective omega-agatoxins.. Nat.Struct.Biol., 1:853-856, 1994. ...https://pdbj.org/mine/summary/1iva
- Agelenopsis aperta, the American funnel-web spider, produces agatoxins. (wikipedia.org)
- Agatoxins are a class of chemically diverse polyamine and peptide toxins which are isolated from the venom of various spiders, in particular the North American funnel-web spider (Agelenopsis aperta), after which agatoxins are named. (t3db.ca)