Méry P F, Lohmann S M, Walter U, Fischmeister R
Laboratoire de Physiologie Cellulaire Cardiaque, Institut National de la Santé et de la Recherche Médicale U-241, Université de Paris-Sud.
Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1197-201. doi: 10.1073/pnas.88.4.1197.
Regulation of cardiac contraction by neurotransmitters and hormones is often correlated with regulation of the L-type Ca2(+)-channel current (ICa) through the opposite actions of two second messengers, cyclic AMP and cyclic GMP. While cyclic AMP stimulation of ICa is mediated by the activation of cyclic AMP-dependent protein kinase, inhibition of ICa by cyclic GMP in frog heart is largely mediated by activation of cyclic AMP phosphodiesterase. The present patch-clamp study reveals that, in rat ventricular cells, cyclic GMP can also regulate ICa via activation of endogenous cyclic GMP-dependent protein kinase (cGMP-PK). Indeed, the effect of cyclic GMP on ICa was mimicked by intracellular perfusion with the proteolytic active fragment of purified cGMP-PK. Moreover, cGMP-PK immunoreactivity was detected in pure rat ventricular myocytes by using a specific polyclonal antibody. These results demonstrate a dual mechanism for the inhibitory action of cyclic GMP in heart, as well as a physiological role for cGMP-PK in the control of mammalian heart function.
神经递质和激素对心脏收缩的调节通常与L型Ca2+通道电流（ICa）的调节相关，这是通过两种第二信使环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）的相反作用实现的。虽然cAMP对ICa的刺激是由环磷酸腺苷依赖性蛋白激酶的激活介导的，但在蛙心中，cGMP对ICa的抑制主要是由环磷酸腺苷磷酸二酯酶的激活介导的。目前的膜片钳研究表明，在大鼠心室细胞中，cGMP也可以通过激活内源性环磷酸鸟苷依赖性蛋白激酶（cGMP-PK）来调节ICa。事实上，用纯化的cGMP-PK的蛋白水解活性片段进行细胞内灌注可模拟cGMP对ICa的作用。此外，通过使用特异性多克隆抗体在纯大鼠心室肌细胞中检测到了cGMP-PK免疫反应性。这些结果证明了cGMP在心脏中抑制作用的双重机制，以及cGMP-PK在控制哺乳动物心脏功能中的生理作用。
