Frontiers | Different pH-sensitivity patterns of 30 sodium channel inhibitors suggest chemically different pools along the...
For this reason, ligand-membrane interactions are as important determinants of inhibitor properties, as ligand-protein ... For this reason, ligand-membrane interactions are as important determinants of inhibitor properties, as ligand-protein ... and/or lipophilic binding sites on the channel). Rescue from the hydrophilic and lipophilic traps can be promoted by alkalic ... interactions. One way to probe this is to modify the pH of the extracellular fluid, which alters the ratio of charged vs. ...https://www.frontiersin.org/articles/10.3389/fphar.2015.00210/full
Indian Patents. 234877:BIARYL SUBSTITUTED 6-MEMBERED HETEROCYCLES AS SODIUM CHANNEL BLOCKERS
Catterall, W. A. Structure and function of voltage-gated sodium and calcium channels. Current Opinion in NeuroUology 1,5-13 ( ... which constitutes the rising phase of the action potential and in turn activates voltage-gated calcium and potassium channels. ... Several regions in the sodium channel secondary structure are involved in interactions with these blockers and most are highly ... Sodium channels are the target of a diverse array of pharmacological agents, including neurotoxins, antiarrhythmics, ...http://www.allindianpatents.com/patents/234877-biaryl-substituted-6-membered-heterocycles-as-sodium-channel-blockers
Marine Drugs | Free Full-Text | µ-Conotoxins Modulating Sodium Currents in Pain Perception and Transmission: A Therapeutic...
µ and µO-CTX are two isoforms that specifically target voltage-gated sodium channels. These, by inducing the entrance of sodium ... In this review, we describe the current knowledge of µ-CTX interacting with the different sodium channels subtypes, the ... Hyperexcitability and mutations of sodium channels are responsible for perception and transmission of inflammatory and ... and voltage-gated potassium channel subtypes of the KV1 family . Recent findings also demonstrated that μ-PIIIA targets the ...http://www.mdpi.com/1660-3397/15/10/295/htm
p75 and TrkA Signaling Regulates Sympathetic Neuronal Firing Patterns via Differential Modulation of Voltage-Gated Currents |...
2001) Nerve growth factor regulates sodium but not potassium channel currents in sympathetic B neurons of adult bullfrogs. J ... Indeed, pharmacological manipulations that increase sodium current promote tonic firing and blockers decrease firing in ... 4). Furthermore, we found that the M-current blocker linopirdine blocked C2-ceramide-dependent induction of phasic firing, ... of threshold current. Pharmacological agents were applied to separate pools of neurons, which were recorded from between 15 min ...http://www.jneurosci.org/content/29/17/5411
Saxitoxin Is a Gating Modifier of hERG K+ Channels | JGP
It inhibits voltage-gated sodium channels by binding to the outer ion conduction pore, and causes rapid neuromuscular paralysis ... as expected for a open state pore blocker). There was no tail current crossover as is seen with some open state blockers that ... A novel extracellular calcium sensing mechanism in voltage-gated potassium ion channels. J. Neurosci. 21:4143-4153. ... STX Modulates hERG K+ Channel Gating. To explore the mechanism of the STX-channel interactions both kinetically and in steady- ...http://jgp.rupress.org/content/121/6/583
Gabapentin For Opiate Withdrawal - Mental Health Daily
... voltage-gated sodium channel currents are weakened. The weakening of voltage-gated sodium channel currents inhibits neuronal ... Research suggests that gabapentin is a strong blocker of N-type calcium channels. Blockers of N-type calcium channels have been ... Interactions: Although gabapentin does not interact with other substances pharmacokinetically, it may interact ... understood to generate analgesic effects through activation of alpha-2 adrenoreceptors and G-protein-coupled potassium channels ...https://mentalhealthdaily.com/2016/11/12/gabapentin-for-opiate-withdrawal/
Alabama to Beijing... and Back: The Search for a Pain Gene
4 Akopian, A. N., Sivilotti, L. & Wood, J. N. A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory ... 2 Kocsis, J. D. & Waxman, S. G. Long-term regenerated nerve fibres retain sensitivity to potassium channel blocking agents. ... 8 Tate, S. et al. Two sodium channels contribute to the TTX-R sodium current in primary sensory neurons. Nat Neurosci 1, 653- ... Peripheral sodium channel blockers became a "holy grail" of pain research. Between 1996 and 1999 three different peripheral ...http://webmail.dana.org/Cerebrum/2018/Alabama_to_Beijing_and_Back_The_Search_for_a_Pain_Gene/
Frontiers | Involvement of gap junction channels in the pathophysiology of migraine with aura | Physiology
Gap junction channels seem to be involved in several ways in the pathophysiology of migraine with aura and emerge as a new ... quinidine and the derivative mefloquine are able to inhibit CSD suggesting an involvement of neuronal connexin36 channels in ... shown to induce headache by activating the trigeminovascular system through the opening of stressed neuronal Pannexin1 channels ... shown to induce headache by activating the trigeminovascular system through the opening of stressed neuronal Pannexin1 channels ...https://www.frontiersin.org/articles/10.3389/fphys.2014.00078/full
Antagonism of Lidocaine Inhibition by Open-Channel Blockers That Generate Resurgent Na Current | Journal of Neuroscience
Human voltage-gated sodium channel mutations that cause inherited neuronal and muscle channelopathies increase resurgent sodium ... express a native blocker), these cells may have a decreased sensitivity to use-dependent clinical agents. ... 2006) Differential lidocaine sensitivity of human voltage-gated potassium channels relevant to the auditory system. Otol ... 1979) Interactions between quaternary lidocaine, the sodium channel gates, and tetrodotoxin. Biophys J 27:39-55. ...http://www.jneurosci.org/content/33/11/4976
Development of models for predicting Torsade de Pointes cardiac arrhythmias using perceptron neural networks | BMC...
Repolarization involves interactions among numerous calcium, sodium, and potassium channels. Nevertheless, potassium channels ... potassium channels generally are separated into the following major categories: the voltage-gated channels with six ... Villoutreix BO, Taboureau O. Computational investigations of hERG channel blockers: new insights and current predictive models ... There are a few drugs that block hERG channels without causing TdP. Verapamil, a potent hERG channel blocker is not associated ...https://bmcbioinformatics.biomedcentral.com/articles/10.1186/s12859-017-1895-2
Congenital long QT syndrome | Orphanet Journal of Rare Diseases | Full Text
Treatment should always begin with β-blockers, unless there are valid contraindications. If the patient has one more syncope ... basis of the disease was identified in the mid-nineties and all the LQTS genes identified so far encode cardiac ion channel ... subunits or proteins involved in modulating ionic currents. Mutations in these genes (KCNQ1, KCNH2, KCNE1, KCNE2, CACNA1c, CAV3 ... The most prevalent forms are LQT1 and LQT2 (due to mutations in potassium channels), and LQT3 (due to a sodium channel mutation ...https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-3-18
Abstracts of Papers at the sixty-second annual meeting of the society of general physiologists | JGP
Intracellular Ca2+ can mediate bimodal regulation of the voltage-gated cardiac sodium channel (NaV1.5) through its C terminus ( ... Whole-cell current measurements have confirmed this observation. Analysis of the single-channel currents allowed us to conclude ... These interactions among intracellular channel proteins are important for understanding regulation of Ca2+ signaling and its ... Structural Determinants of Phosphoinositide Regulation of M-type Potassium Channels. CIRIA C. HERNANDEZ and MARK S. SHAPIRO, ...http://jgp.rupress.org/content/132/1/3a
Analgesic - Wikipedia
Some novel and investigational analgesics include subtype-selective voltage-gated sodium channel blockers such as funapide and ... N-type calcium-channel blocker.. Intrathecal.. Protein binding = 50%; half-life = 2.9-6.5 hours; excretion = urine (,1%). ... Comes in sodium, potassium and diethylamine (topically used as a gel) salt forms; sparingly soluble in water but soluble in ... Psychotropic agents. Other psychotropic analgesic agents include ketamine (an NMDA receptor antagonist), clonidine and ...https://en.wikipedia.org/wiki/Analgetics
The Centrality of Ca(2+) Signaling and Cytoskeleton Involving Calmodulin Kinases and Ryanodine Receptors in Cardiac Failure,...
NCX, sodium/calcium exchanger.. Calcium enters the myocyte through voltage-gated L-type Ca2+ channels; this triggers release of ... Further, he observes that with the exception of so-called beta blockers, none of the current anti-arrhythmic drugs have been ... Cardiac ATP-sensitive potassium channels (KATP channels) contain a potassium pore and an enzyme complex that participate in ... Differential regulated interactions of calcium/calmodulin-dependent protein kinase II with isoforms of voltage-gated calcium ...https://pharmaceuticalintelligence.com/2013/09/08/the-centrality-of-ca2-signaling-and-cytoskeleton-involving-calmodulin-kinases-and-ryanodine-receptors-in-cardiac-failure-arterial-smooth-muscle-post-ischemic-arrhythmia-similarities-and-differen/
1997) Blockade of the voltage-gated potassium channel Kv1.3 inhibits immune responses in vivo. J Immunol 158: 5120-5128. ... or ionic current in cultured microglia (i.e., Kv1.2, Kv1.3, Kv1.5, Kv1.6, and SK4). Blocker concentrations were chosen to ... Five K channel blockers were used at sufficiently high concentrations to block the main channel of interest (Table 2), as ... Neurons were washed in PBS (5 min, two times), permeabilized in Triton X-100 (0.01%) and sodium citrate (1%) on ice, washed ...http://www.jneurosci.org/content/25/31/7139
Dopamine and Aging: Intersecting Facets | SpringerLink
Rescue of mesencephalic dopaminergic neurons in culture by low-level stimulation of voltage-gated sodium channels. J Neurosci ... Wei L, Yu SP, Gottron F et al (2003) Potassium channel blockers attenuate hypoxia- and ischemia-induced neuronal death in vitro ... Wang JW, Humphreys JM, Phillips JP et al (2000) A novel leg-shaking Drosophila mutant defective in a voltage-gated K+ current ... Salgado E, Murray DB, Lloyd D (2002) Some antidepressant agents (Li+, monoamine oxidase type A inhibitors) perturb the ...https://link.springer.com/article/10.1007%2Fs11064-008-9858-7
Molecular characterization of the cyclic nucleotide-gated cation channel of bovine rod outer segments - UBC Library Open...
... ion channels 10 1.3.1 Sodium channels 13 1.3.2 Calcium channels 15 1.3.3 Potassium channels 18 1.3.4 Cyclic nucleotide-gated ... Quandt, F.N., Nicol, G.D., Schnetkamp, P.P.M. (1991) Voltage-dependent gating and block of the cyclic-GMP-dependent current in ... The system presented here will also enable further characterization of the CNG channel subunit interactions. Ultimately, large ... The most potent blocker of the cGMP-dependent channel is the /-stereoisomer of cisdiltiazem (Koch and Kaupp, 1985). Work with ...https://open.library.ubc.ca/cIRcle/collections/ubctheses/831/items/1.0094703
... sodium channel blockers, exogenous potassium, or potassium channel openers) improve survival has been published. ... protein in various heterologous systems confirmed this protein to be a voltage-gated potassium channel protein subunit, which ... slowly activating potassium current. HERG. human ether-a-go-go-related gene. IKr. delayed rectifier potassium current. ... However, long-term potassium therapy with associated potassium-sparing agents has been unable to keep the serum potassium above ...http://dmd.aspetjournals.org/content/29/4/574
Advances in Neurobiology of the Neuromuscular Junction:Implications for the Anesthesiologist | Anesthesiology | ASA Publications
... including voltage-gated and Ca2+-activated potassium channels. The potassium channels are likely to limit the duration of nerve ... In contrast, the action of steroidal neuromuscular blockers, agents dependent on organ elimination, is prolonged in the elderly ... A non-inactivating sodium current and the effect of extracellular pH. Muscle Nerve 1987; 10: 363-74Lehmann-Horn, F Kuther, G ... An open channel blocker of the nAChR, quinidine sulfate, is therapeutically efficacious in SCCMS because it normalizes the open ...http://anesthesiology.pubs.asahq.org/article.aspx?articleid=1944783
Nifedipine - DrugBank
It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive ... Calcium Channel Blockers (Dihydropyridine). *Calcium Channel Blockers and Diuretics. *Cardiovascular Agents. *Contraceptive ... Voltage-gated potassium channel activity. Specific Function. Voltage-gated potassium channel that mediates transmembrane ... 4-dihydropyridine calcium channel blocker. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L- ...https://www.drugbank.ca/drugs/DB01115
Protocols and Video Articles Authored by Alessandro Mugelli (Translated to German)
... current were used. All calcium channel blockers, at concentrations blocking less than 30% of L-type Ca(2+) current, inhibited a ... opposite to most voltage-gated channels. Recently, electrophysiological and molecular data demonstrated that f-channels are ... whereas the rapid delayed rectifier potassium current (I(Kr)), pacemaker current (I(f)), and L-type calcium current (I(Ca,L)) ... channels). In particular, we focus on the role of the "late sodium current" (INaL), a sustained component of the fast Na(+) ...https://www.jove.com/author/Alessandro_Mugelli?language=German
Taking Lamictal (Lamotrigine) For Anxiety Disorders: Does It Help?
Potassium (K+) channel modulation: In addition to blocking various voltage-gated sodium and calcium channels, lamotrigine ... Agents with similar pharmacodynamics to lamotrigine (Na+ channel blockers), including carbamazepine (20-40 mg/kg) and riluzole ... lamotrigine's action as a voltage-gated sodium channel blocker may generate a more substantial anxiolytic effect than other ... As of current, evidence suggests that lamotrigine's calcium channel antagonism may be more significant than initially suspected ...https://mentalhealthdaily.com/2016/10/04/lamictal-lamotrigine-for-anxiety-disorders/?replytocom=149006
... channels, resulting in a transient KCa current. The resulting membrane hyperpolarization reduces voltage-dependent Ca2+ channel ... Cardiac and skeletal muscle RyR channels are redox sensitive and are activated by oxidizing agents, including H2O2 (42). ROS ... MnTMPyP, thapsigargin, a sarcoplasmic reticulum Ca2+-ATPase blocker that inhibits Ca2+ sparks, and iberiotoxin, a KCa channel ... 5-trisphosphate-gated Ca2+ channels. Although the physiological functions of Ca2+ waves have been less well described, Ca2+ ...http://ajpcell.physiology.org/content/290/4/C964