Mechanism of sodium channel block in crayfish giant axons by 711389-S, a new potent antiarrhythmic drug

I. Muramatsu, Mami Noda, M. Nishio, M. Fujiwara

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The effects of 711389-S, a new antiarrhythmic drug, on the sodium channel of crayfish giant axon were studied using microelectrode and sucrose-gap voltage-clamp techniques. When applied externally, 711389-S suppressed the action potential and the rate of rise without affecting the resting membrane potential. Voltage-clamp experiments revealed that 711389-S inhibits the sodium current more selectively than the potassium current and that the inhibition is more evident with internal rather than external application. The inhibitory effect of internally applied 711389-S on sodium current was enhanced at less negative holding potentials. 711389-S also shifted the steady-state inactivation curve in the direction of hyperpolarization. Use-dependent block became evident in the 711389-S-treated axons; this block resulted from an increase in the slow inactivating state during repetitive depolarization and from a slow recovery from the inactivated state during the pulse interval. 711389-S produced an additional inhibition when sodium channels were open at large depolarizations. The additional inhibition could be reversed by small depolarizations that opened the sodium channels. These observations suggest that 711389-S binds the resting, inactivated and open states of the sodium channel, resulting in a reduction of sodium channel availability. 711389-S also shifted the voltage dependence of peak sodium conductance toward a less negative potential.

Original languageEnglish
Pages (from-to)269-276
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume242
Issue number1
Publication statusPublished - Jan 1 1987

Fingerprint

711389-S
Astacoidea
Sodium Channels
Anti-Arrhythmia Agents
Axons
Sodium
Microelectrodes
Patch-Clamp Techniques

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Mechanism of sodium channel block in crayfish giant axons by 711389-S, a new potent antiarrhythmic drug. / Muramatsu, I.; Noda, Mami; Nishio, M.; Fujiwara, M.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 242, No. 1, 01.01.1987, p. 269-276.

Research output: Contribution to journalArticle

@article{ffb4a243218146b0833c995421ff7c82,
title = "Mechanism of sodium channel block in crayfish giant axons by 711389-S, a new potent antiarrhythmic drug",
abstract = "The effects of 711389-S, a new antiarrhythmic drug, on the sodium channel of crayfish giant axon were studied using microelectrode and sucrose-gap voltage-clamp techniques. When applied externally, 711389-S suppressed the action potential and the rate of rise without affecting the resting membrane potential. Voltage-clamp experiments revealed that 711389-S inhibits the sodium current more selectively than the potassium current and that the inhibition is more evident with internal rather than external application. The inhibitory effect of internally applied 711389-S on sodium current was enhanced at less negative holding potentials. 711389-S also shifted the steady-state inactivation curve in the direction of hyperpolarization. Use-dependent block became evident in the 711389-S-treated axons; this block resulted from an increase in the slow inactivating state during repetitive depolarization and from a slow recovery from the inactivated state during the pulse interval. 711389-S produced an additional inhibition when sodium channels were open at large depolarizations. The additional inhibition could be reversed by small depolarizations that opened the sodium channels. These observations suggest that 711389-S binds the resting, inactivated and open states of the sodium channel, resulting in a reduction of sodium channel availability. 711389-S also shifted the voltage dependence of peak sodium conductance toward a less negative potential.",
author = "I. Muramatsu and Mami Noda and M. Nishio and M. Fujiwara",
year = "1987",
month = "1",
day = "1",
language = "English",
volume = "242",
pages = "269--276",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "1",

}

TY - JOUR

T1 - Mechanism of sodium channel block in crayfish giant axons by 711389-S, a new potent antiarrhythmic drug

AU - Muramatsu, I.

AU - Noda, Mami

AU - Nishio, M.

AU - Fujiwara, M.

PY - 1987/1/1

Y1 - 1987/1/1

N2 - The effects of 711389-S, a new antiarrhythmic drug, on the sodium channel of crayfish giant axon were studied using microelectrode and sucrose-gap voltage-clamp techniques. When applied externally, 711389-S suppressed the action potential and the rate of rise without affecting the resting membrane potential. Voltage-clamp experiments revealed that 711389-S inhibits the sodium current more selectively than the potassium current and that the inhibition is more evident with internal rather than external application. The inhibitory effect of internally applied 711389-S on sodium current was enhanced at less negative holding potentials. 711389-S also shifted the steady-state inactivation curve in the direction of hyperpolarization. Use-dependent block became evident in the 711389-S-treated axons; this block resulted from an increase in the slow inactivating state during repetitive depolarization and from a slow recovery from the inactivated state during the pulse interval. 711389-S produced an additional inhibition when sodium channels were open at large depolarizations. The additional inhibition could be reversed by small depolarizations that opened the sodium channels. These observations suggest that 711389-S binds the resting, inactivated and open states of the sodium channel, resulting in a reduction of sodium channel availability. 711389-S also shifted the voltage dependence of peak sodium conductance toward a less negative potential.

AB - The effects of 711389-S, a new antiarrhythmic drug, on the sodium channel of crayfish giant axon were studied using microelectrode and sucrose-gap voltage-clamp techniques. When applied externally, 711389-S suppressed the action potential and the rate of rise without affecting the resting membrane potential. Voltage-clamp experiments revealed that 711389-S inhibits the sodium current more selectively than the potassium current and that the inhibition is more evident with internal rather than external application. The inhibitory effect of internally applied 711389-S on sodium current was enhanced at less negative holding potentials. 711389-S also shifted the steady-state inactivation curve in the direction of hyperpolarization. Use-dependent block became evident in the 711389-S-treated axons; this block resulted from an increase in the slow inactivating state during repetitive depolarization and from a slow recovery from the inactivated state during the pulse interval. 711389-S produced an additional inhibition when sodium channels were open at large depolarizations. The additional inhibition could be reversed by small depolarizations that opened the sodium channels. These observations suggest that 711389-S binds the resting, inactivated and open states of the sodium channel, resulting in a reduction of sodium channel availability. 711389-S also shifted the voltage dependence of peak sodium conductance toward a less negative potential.

UR - http://www.scopus.com/inward/record.url?scp=0023184112&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023184112&partnerID=8YFLogxK

M3 - Article

C2 - 2441025

AN - SCOPUS:0023184112

VL - 242

SP - 269

EP - 276

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 1

ER -