James A F, Xie L H, Horie M
International Research Laboratories, Ciba-Geigy Japan Ltd., Takarazuka, Japan.
Jpn J Physiol. 1994;44 Suppl 2:S227-30.
The effects of endothelin-1 (ET-1) on whole-cell cardiac PKA-dependent Cl- currents (ICl) were investigated using patch clamp techniques. ET-1 inhibited the isoproterenol-induced ICl with a half-maximally effective concentration of approximately 1 nM. ET-1 also inhibited the forskolin-induced current in a similar concentration range. The effects of ET-1 were abolished by pre-treatment of the cells with pertussis toxin. Since ET-1 was ineffective at inhibiting the ICl induced by internal dialysis with cyclic AMP, it is unlikely that the Gi-protein had a direct effect on channel gating or phosphorylation of the channel by PKA. It is concluded that ET-1 inhibited the cardiac PKA-dependent ICl by attenuating activation of adenylate cyclase and that this effect was mediated by a pertussis toxin-sensitive G-protein, presumably Gi.
采用膜片钳技术研究了内皮素 -1（ET -1）对全细胞心脏依赖蛋白激酶A（PKA）的氯离子电流（ICl）的影响。ET -1抑制异丙肾上腺素诱导的ICl，其半数有效浓度约为1 nM。ET -1在相似浓度范围内也抑制福斯高林诱导的电流。用百日咳毒素预处理细胞可消除ET -1的作用。由于ET -1对内源性环磷酸腺苷透析诱导的ICl无抑制作用，因此G蛋白不太可能直接影响通道门控或PKA对通道的磷酸化。得出的结论是，ET -1通过减弱腺苷酸环化酶的激活来抑制心脏依赖PKA的ICl，并且这种作用是由百日咳毒素敏感的G蛋白（可能是Gi）介导的。
