Effect of procaine and calcium ions on slow sodium inactivation in the frog ranvier node membrane

Bi, Khodorov; Shishkova, L. D.; Peganov, É. M.

doi:10.1007/bf00802462

Cited by 10 publications

(10 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The findings of Khodorov et al (1974Khodorov et al ( , 1976) that certain local anesthetics induce a slow inactivation of sodium channels in frog node raises the possibility that NEM is acting by virtue of "pharmacological" properties rather than by reaction with sulfhydryl residues. Testing several anesthetics, Khodorov et al (1976) found that only the tertiary amines produced slow inactivation.…”

Section: Discussionmentioning

confidence: 99%

Slow sodium inactivation in nerve after exposure to sulhydryl blocking reagents.

Shrager¹

1977

The Journal of General Physiology

View full text Add to dashboard Cite

A B S T R A C T Exposure to N-ethylmaleimide (NEM), a reagent that binds covalently to protein sulfhydryl groups, results in a specific reduction in sodium conductance in crayfish axons. Resting potential, the delayed rise in potassium conductance, and the selectivity of the sodium channel are unaffected. Sodium currents are only slightly increased by hyperpolarizing prepulses of up to 50 ms duration, but can be restored to about 70% of their value before treatment if this duration is increased to 300-800 ms. The time to peak sodium current and the time constant of decay of sodium tail currents are unaffected by NEM, suggesting that the sodium activation system remains unaltered. Kinetic studies suggest that NEM reacts with a "slow" sodium inactivation system that is present in normal axons and that may be seen after depolarization produced by lowering the holding potential or increasing the external potassium concentration. NEM also perturbs the fast h inactivation system, and in a potential-dependent manner. At small depolarizations 7h is decreased, while at strong depolarizations it is increased over control values. Experiments with structural analogs of NEM suggest that sulfhydryl block is involved, but do not rule out an action similar to that of local anesthetics, pChloromercuriphenylsulfonic acid (PCMBS), another reagent with high specificity for SH groups, also blocks sodium currents, but restoration with prolonged hyperpolarizations is not possible.

show abstract

Section: Discussionmentioning

confidence: 99%

Slow sodium inactivation in nerve after exposure to sulhydryl blocking reagents.

Shrager¹

1977

The Journal of General Physiology

View full text Add to dashboard Cite

show abstract

“…The hypothesis centered around earlier findings that the binding of local anesthetics promoted inactivation gating of sodium channels and that block was reduced by procedures that alleviated inactivation, i.e., membrane hyperpolarization (120,258,259,321,680) or pronase treatment (83). In the modulated receptor hypothesis, which is analogous to the model for allosteric modulation of enzyme activity proposed by Monod et al (424), local anesthetics preferentially bind to the inactivated state of sodium channels and, in turn, local anesthetic binding promotes inactivation (258).…”

Section: Modulated Receptor Hypothesis For Drug Blockmentioning

confidence: 98%

hERG K⁺Channels: Structure, Function, and Clinical Significance

Vandenberg

Perry

Perrin

et al. 2012

Physiological Reviews

607

773

View full text Add to dashboard Cite

The human ether-a-go-go related gene (hERG) encodes the pore-forming subunit of the rapid component of the delayed rectifier K(+) channel, Kv11.1, which are expressed in the heart, various brain regions, smooth muscle cells, endocrine cells, and a wide range of tumor cell lines. However, it is the role that Kv11.1 channels play in the heart that has been best characterized, for two main reasons. First, it is the gene product involved in chromosome 7-associated long QT syndrome (LQTS), an inherited disorder associated with a markedly increased risk of ventricular arrhythmias and sudden cardiac death. Second, blockade of Kv11.1, by a wide range of prescription medications, causes drug-induced QT prolongation with an increase in risk of sudden cardiac arrest. In the first part of this review, the properties of Kv11.1 channels, including biogenesis, trafficking, gating, and pharmacology are discussed, while the second part focuses on the pathophysiology of Kv11.1 channels.

show abstract

“…It is well established that in the presence of local anesthetics, iNa recovers with two distinct time courses : a normal phase of recovery, and a second, much slower phase of recovery (Khodorov et al ., 1974(Khodorov et al ., , 1976Courtney, 1975). Within the context of a modulated-receptor hypothesis, slow recovery is believed to result from restricted diffusion of drug molecules from the receptor via a hydrophobic pathway .…”

Section: Drug-induced Changes In Ica Reactivationmentioning

confidence: 99%

Interactions of organic calcium channel antagonists with calcium channels in single frog atrial cells.

Uehara¹,

Hume²

1985

The Journal of General Physiology

182

128

View full text Add to dashboard Cite

Inhibition of whole-cell calcium currents in enzymatically dispersed frog atrial myocytes by D-600, diltiazem, and nifedipine was studied using a single-micropipette voltage-clamp technique. The objective of these experiments was to test the applicability of a modulated-receptor hypothesis similar to that proposed for local anesthetic interactions with sodium channels to account for the tonic and frequency-dependent interactions of these organic compounds with myocardial calcium channels . Data consistent with such a hypothesis include: (a) prominent use-dependent block of ica by D-600 and diltiazem, which are predominantly charged at physiological pH; (b) ica block by an externally applied, permanently charged dihydropyridine derivative is greatly attenuated ; (c) all three antagonists produce large negative shifts in the voltage dependence of " availability ; (d) block of ic, by these compounds is state-dependent ; (e) reactivation of ica in the presence of all three antagonists is biexponential, which suggests that drug-free channels recover with a normal time course and drug-bound channels recover more slowly ; and (f) the kinetics of the drug-induced slow iCa recovery process may be determined largely by factors such as size and molecular weight, in addition to lipid solubility of the compounds. Experiments in which the pH was modified, however, reveal some important differences for the interaction of organic calcium antagonists with myocardial calcium channels . Acidification, in addition to changing the proportion of charged and neutral antagonist in solution, was found to selectively antagonize tonic inhibition of ica by diltiazem and nifedipine, without changing the kinetics of the drug-induced slow ica reactivation process. It is concluded that two distinct receptor sites may be involved in block of ica by some of these compounds: a proton-accessible site and a proton-inaccessible site .

show abstract

Effect of procaine and calcium ions on slow sodium inactivation in the frog ranvier node membrane

Cited by 10 publications

References 14 publications

Slow sodium inactivation in nerve after exposure to sulhydryl blocking reagents.

Slow sodium inactivation in nerve after exposure to sulhydryl blocking reagents.

hERG K⁺Channels: Structure, Function, and Clinical Significance

Interactions of organic calcium channel antagonists with calcium channels in single frog atrial cells.

Contact Info

Product

Resources

About

Effect of procaine and calcium ions on slow sodium inactivation in the frog ranvier node membrane

Cited by 10 publications

References 14 publications

Slow sodium inactivation in nerve after exposure to sulhydryl blocking reagents.

Slow sodium inactivation in nerve after exposure to sulhydryl blocking reagents.

hERG K+Channels: Structure, Function, and Clinical Significance

Interactions of organic calcium channel antagonists with calcium channels in single frog atrial cells.

Contact Info

Product

Resources

About

hERG K⁺Channels: Structure, Function, and Clinical Significance