Effects of a novel, potent benzothiazepine Ca2+ channel antagonist, DTZ323, on guinea-pig ventricular myocytes
Effects of a novel, potent benzothiazepine Ca2+ channel antagonist, DTZ323, on guinea-pig ventricular myocytes
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DOI：
10.1016/s0014-2999(97)00119-2
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发表时间：
1997-05-01
影响因子：
5
通讯作者：
Nagao, T
中科院分区：
文献类型：
--
作者：
Kurokawa, J;AdachiAkahane, S;Nagao, T
The effects of a 1,5-benzothiazepine derivative, (+)-cis-3-(acetyloxy)-5-[2-[[2-(3,4-dimethoxyphenyl)ethyl]- methylamino]ethyl]-2,3- dihydro-2-(4-methyoxyphenyl)-1,5-benzothiazepine-4(5H)-one (DTZ323), on membrane currents were investigated in guinea-pig ventricular myocytes using the whole-cell patch-clamp technique. DTZ323 suppressed the L-type Ca2+ channel currents (I-Ca(L)) more selectively than the T-type Ca2+ channel and the Na+ channel currents. DTZ323 inhibited I-Ca(L) in a use- and a voltage-dependent manner with 24 times higher potency than that of diltiazem. Rate of recovery of I-Ca(L) from the conditioned block by DTZ323 was faster compared with diltiazem and verapamil, and was steeply dependent on the holding potential at resting membrane potential range in ventricular myocytes (-90 to -60 mV). Our results suggest that DTZ323 is a selective Ca2+ channel antagonist, the most potent among the 1,5-benzothiazepine Ca2+ channel antagonists, and that the voltage- and use-dependent effect of DTZ323 on I-Ca(L) is due to the steep voltage dependence of the rate of dissociation from the cardiac L-type Ca2+ channels.
