Molecular mechanism of allosteric modification of voltage-dependent sodium channels by local anesthetics

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Molecular mechanism of allosteric modification of voltage-dependent sodium channels by local anesthetics

The hallmark of many intracellular pore blockers such as tetra-alkylammonium compounds and local anesthetics is their ability to allosterically modify the movement of the voltage sensors in voltage-dependent ion channels. For instance, the voltage sensor of domain III is specifically stabilized in the activated state when sodium currents are blocked by local anesthetics. The molecular mechanism...

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The role of inactivation in the cumulative blockage of voltage-dependent sodium channels by local anesthetics and antiarrythmics.

Previously published results (Khodorov 1973; Khodorov et al. 1974, 1976; Zaborovskaya 1976) showed that along with a decrease in the maximum sodium permeability ('tonic block') the tertiary amine local anesthetics (LA), procaine and trimecain cause a drastic slowing of Na channel reactivation after membrane depolarization. This effect ("drug-induced slow Na inactivation") underlies a use-depend...

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Molecular mechanism of inhibition of firefly luminescence by local anesthetics.

The kinetics of the action of local anesthetics upon firefly luciferin and luciferase systems is presented. Clinical concentrations of local anesthetics inhibited this ATP-induced luminescence in a dose-dependent manner. From the effects of temperature and pH upon the inhibitory action of the local anesthetics, it is concluded that hydrophobic ligand-enzyme interaction is the predominant cause ...

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Molecular mechanism of voltage-dependent potentiation of KCNH potassium channels

EAG-like (ELK) voltage-gated potassium channels are abundantly expressed in the brain. These channels exhibit a behavior called voltage-dependent potentiation (VDP), which appears to be a specialization to dampen the hyperexitability of neurons. VDP manifests as a potentiation of current amplitude, hyperpolarizing shift in voltage sensitivity, and slowing of deactivation in response to a depola...

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Ketamine blockade of voltage-gated sodium channels: evidence for a shared receptor site with local anesthetics.

BACKGROUND The general anesthetic ketamine is known to be an N-methyl-D-aspartate receptor blocker. Although ketamine also blocks voltage-gated sodium channels in a local anesthetic-like fashion, little information exists on the molecular pharmacology of this interaction. We measured the effects of ketamine on sodium channels. METHODS Wild-type and mutant (F1579A) recombinant rat skeletal mus...

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ژورنال

عنوان ژورنال: Journal of General Physiology

سال: 2010

ISSN: 1540-7748,0022-1295

DOI: 10.1085/jgp.201010438