Electrophysiological effects of SN-6, a novel Na+/Ca2+ exchange inhibitor on membrane currents in guinea pig ventricular myocytes.
We examined the effect of SN-6 on the Na+/Ca2+ exchanger (NCX) current (I(NCX)) and other membrane currents in isolated guinea pig ventricular myocytes using the whole-cell voltage clamp technique. SN-6 suppressed the bidirectional I(NCX) in a concentration-dependent manner. The IC50 values of SN-6 were 2.3 microM and 1.9 microM for the outward and inward components of the bidirectional I(NCX), respectively. On the other hand, SN-6 suppressed the unidirectional outward I(NCX) more potently than the inward I(NCX), with an IC(50) value of 0.6 microM. SN-6 at 10 microM inhibited the unidirectional inward I(NCX) by only 22.4 +/- 3.1%. SN-6 suppressed I(NCX) more potentially when intracellular Na+ concentration became higher. SN-6 inhibited I(Na), I(Ca), I(Kr), I(Ks), and I(K1) by about 13%, 34%, 33%, 18%, and 13%, respectively. SN-6 shortened the action potential duration (APD) by about 34% and 25% at APD(50) and APD(90), respectively. These results indicate that SN-6 inhibits NCX in a similar manner to that of KB-R7943. SN-6 and KB-R7943 inhibit the unidirectional outward I(NCX) more potently than the unidirectional inward I(NCX). Both drugs inhibit NCX in an intracellular Na+ concentration-dependent manner. However, SN-6 affected other membrane currents less potently than KB-R7943.
Niu
Chun-Feng
CF
Department of Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Hondayama, Hamamatsu, Shizuoka, 431-3192, Japan.
Watanabe
Yasuhide
Y
Iwamoto
Takahiro
T
Yamashita
Kanna
K
Satoh
Hiroshi
H
Urushida
Tuyoshi
T
Hayashi
Hideharu
H
Kimura
Junko
J
D000818:Animals; D001593:Benzyl Compounds / Q000494:pharmacology*; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects*; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*; D053778:Thiazolidines / Q000494:pharmacology*; D016276:Ventricular Function
C487681:2-(4-(4-nitrobenzyloxy)benzyl)thiazolidine-4-carboxylic acid ethyl ester; D001593:Benzyl Compounds; D019831:Sodium-Calcium Exchanger; D053778:Thiazolidines