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Block of NA+ and K+ currents in rat ventricular myocytes by quinacainol and quinidine.
Clin Exp Pharmacol Physiol. 2005 Jan-Feb; 32(1-2):60-5.CE

Abstract

1. The electrophysiological actions of quinacainol were investigated on sodium (I(Na)), transient outward (i(to)) and sustained-outward plateau (iKsus) potassium currents in rat isolated cardiac myocytes using the whole-cell patch-clamp technique and compared with quinidine. 2. Quinacainol blocked sodium currents in a concentration-dependent manner and with a potency similar to that of quinidine (mean (+/-SEM) EC50 50+/-12 vs 95+/-25 micromol/L for quinidine and quinacainol, respectively). However, quinacainol had a considerably prolonged onset and recovery from block compared with quinidine. 3. Neither quinacainol nor quinidine significantly changed the steady state voltage dependence of activation of sodium currents. Quinidine produced a hyperpolarizing shift in the voltage dependence for sodium current inactivation, but no such shift was observed with quinacainol at doses that produced a substantial current block. 4. Although quinacainol did not effectively block voltage-dependent potassium currents, even at concentrations as high as 1.5 mmol/L, quinidine, at a half-maximal sodium channel-blocking concentration, reduced peak i(to) current amplitude, increased the rate of inactivation of i(to) and blocked iKsus. 5. These results indicate that quinacainol, a quinidine analogue, blocks sodium currents in cardiac myocytes with little effect on i(to) or iKsus potassium currents, which suggests that quinacainol may be exerting class 1c anti-arrhythmic actions.

Authors+Show Affiliations

Pugsley MK
Department of Pharmacology, Forest Research Institute, Jersey City, New Jersey, USA.
Walker MJ
No affiliation info available
Saint DA
No affiliation info available

MeSH

AnimalsAnti-Arrhythmia AgentsDose-Response Relationship, DrugElectrophysiologyHeart VentriclesIn Vitro TechniquesMaleMembrane PotentialsMyocytes, CardiacPotassium Channel BlockersPotassium ChannelsQuinidineQuinolinesRatsRats, WistarSodium Channel BlockersSodium ChannelsSolutions

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15730436

Citation

Pugsley, Michael K., et al. "Block of NA+ and K+ Currents in Rat Ventricular Myocytes By Quinacainol and Quinidine." Clinical and Experimental Pharmacology & Physiology, vol. 32, no. 1-2, 2005, pp. 60-5.
Pugsley MK, Walker MJ, Saint DA. Block of NA+ and K+ currents in rat ventricular myocytes by quinacainol and quinidine. Clin Exp Pharmacol Physiol. 2005;32(1-2):60-5.
Pugsley, M. K., Walker, M. J., & Saint, D. A. (2005). Block of NA+ and K+ currents in rat ventricular myocytes by quinacainol and quinidine. Clinical and Experimental Pharmacology & Physiology, 32(1-2), 60-5.
Pugsley MK, Walker MJ, Saint DA. Block of NA+ and K+ Currents in Rat Ventricular Myocytes By Quinacainol and Quinidine. Clin Exp Pharmacol Physiol. 2005 Jan-Feb;32(1-2):60-5. PubMed PMID: 15730436.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Block of NA+ and K+ currents in rat ventricular myocytes by quinacainol and quinidine. AU - Pugsley,Michael K, AU - Walker,Michael J A, AU - Saint,David A, PY - 2005/2/26/pubmed PY - 2005/6/9/medline PY - 2005/2/26/entrez SP - 60 EP - 5 JF - Clinical and experimental pharmacology & physiology JO - Clin Exp Pharmacol Physiol VL - 32 IS - 1-2 N2 - 1. The electrophysiological actions of quinacainol were investigated on sodium (I(Na)), transient outward (i(to)) and sustained-outward plateau (iKsus) potassium currents in rat isolated cardiac myocytes using the whole-cell patch-clamp technique and compared with quinidine. 2. Quinacainol blocked sodium currents in a concentration-dependent manner and with a potency similar to that of quinidine (mean (+/-SEM) EC50 50+/-12 vs 95+/-25 micromol/L for quinidine and quinacainol, respectively). However, quinacainol had a considerably prolonged onset and recovery from block compared with quinidine. 3. Neither quinacainol nor quinidine significantly changed the steady state voltage dependence of activation of sodium currents. Quinidine produced a hyperpolarizing shift in the voltage dependence for sodium current inactivation, but no such shift was observed with quinacainol at doses that produced a substantial current block. 4. Although quinacainol did not effectively block voltage-dependent potassium currents, even at concentrations as high as 1.5 mmol/L, quinidine, at a half-maximal sodium channel-blocking concentration, reduced peak i(to) current amplitude, increased the rate of inactivation of i(to) and blocked iKsus. 5. These results indicate that quinacainol, a quinidine analogue, blocks sodium currents in cardiac myocytes with little effect on i(to) or iKsus potassium currents, which suggests that quinacainol may be exerting class 1c anti-arrhythmic actions. SN - 0305-1870 UR - https://www.unboundmedicine.com/medline/citation/15730436/Block_of_NA+_and_K+_currents_in_rat_ventricular_myocytes_by_quinacainol_and_quinidine_ DB - PRIME DP - Unbound Medicine ER -