Tanaka Y, Aida M, Tanaka H, Shigenobu K, Toro L
Department of Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 1998 Jun;357(6):705-8. doi: 10.1007/pl00005228.
Large conductance, voltage- and Ca2+-sensitive K+ (maxi-K(Ca)) channels play an important role in the regulation of vascular smooth muscle excitability and contractility. The activity of maxi-K(Ca) channels is modified by a variety of intracellular messengers including cGMP, as well as by voltage and Ca2+. In the present study, we investigated the functional relevance of maxi-K(Ca) channels in atrial natriuretic peptide (ANP)-mediated vasorelaxation in the isolated rat mesenteric artery. ANP produced concentration-dependent relaxation in the de-endothelialized rat mesenteric artery. Iberiotoxin, a specific blocker of maxi-K(Ca) channels, greatly attenuated the ANP-induced vasorelaxation. Similarly, a large portion of the vascular relaxation induced by 8-Bromo-cGMP, a membrane permeable analogue of cGMP, was inhibited by iberiotoxin. These results indicate that activation of maxi-K(Ca) channels contributes substantially to the vascular relaxation produced by ANP in the rat mesenteric artery. Intracellular cGMP, increased by ANP, and the subsequent activation of cGMP-dependent protein kinase (PKG) may play a central role in the activation of maxi-K(Ca) channels in the ANP-produced vascular relaxation.
大电导、电压和Ca2+敏感的K+（大电导钙激活钾通道，maxi-K(Ca)）通道在调节血管平滑肌兴奋性和收缩性方面发挥着重要作用。maxi-K(Ca)通道的活性受到包括cGMP在内的多种细胞内信使的调节，同时也受电压和Ca2+的影响。在本研究中，我们调查了maxi-K(Ca)通道在心房利钠肽（ANP）介导的离体大鼠肠系膜动脉血管舒张中的功能相关性。ANP在去内皮的大鼠肠系膜动脉中产生浓度依赖性舒张。大电导钙激活钾通道特异性阻断剂iberiotoxin大大减弱了ANP诱导的血管舒张。同样，cGMP的膜通透性类似物8-溴-cGMP诱导的大部分血管舒张也被iberiotoxin抑制。这些结果表明，maxi-K(Ca)通道的激活在大鼠肠系膜动脉中对ANP产生的血管舒张起重要作用。ANP增加的细胞内cGMP以及随后的cGMP依赖性蛋白激酶（PKG）激活可能在ANP产生的血管舒张中maxi-K(Ca)通道的激活中起核心作用。
