佛波脂及Microcystine-LR对sHRsp内脏阻力血管平滑肌钙通道的影响

The Effects of Phorbol 12-Myristate 13-Acetate and Microcystine-LR on Calcium Channel in Resistance Vascular Smooth Muscle Cells in SHRsp

目的研究佛波脂(phorbol 12-myristate 13-acetate,PMA)及microcys-tine-LR(MCYST-LR)对卒中易感型自发性高血压大鼠(SHRsp)及常压对照Wistar大鼠肠系膜动脉A4-A5段分支阻力血管平滑肌电压依赖性钙通道的影响。方法采用膜片箝全细胞钡电流方式记录钙通道的活动。结果佛波脂激活蛋白激酶C(PKC)或MCYST-LR抑制细胞蛋白磷酸酶(PPⅠA、PPⅡA)而相对增加磷酸化过程,均可激活内脏阻力血管平滑肌电压依赖性钙通道。结论 PMA的激活效应,在SHRsp,是使开放的L型钙通道活动显著增强,T型钙通道活动略有增加;而在Wistar大鼠,则以T型钙电流增加为主。MCYST-LR仅使SHRsp的L型钙通道活动显著增强。提示在分析高血压的外周阻力增高机制时,应进一步分析PKC和磷酸化机制对钙通道各电流成分的影响。

Objective To investigate the effects of phorbol 12-myristate 13-acetate (PMA) and microcystine-LR (MCYST-LR) on the whole-cell barium currents of voltage-dependent calcium channels (VDCs) of the resistance vascular smooth muscle cells (VSMC) from the A4A5 branches of mesenteric artery in stroke-prone spontaneously hypertensive rats (SHRsp) and its normotensive control Wistar rats. Methods Using the whole-cell Ba^(2+) current recording of the patch clamp technique. Results It was found that PMA, a protein kinase C (PKC) agonist or MCYST-LR, a protein phosphatase IA and IIA inhibitor by which the en- hancement of phosphorylation induced could apparenlty activate the VDCs of the visceral resistance VSMC. Conclusions This activation would be significantly potentiated during hypertension, in which the increase of L-type calcium channel openings induced by PMA was obviously manifest, as the T-type calcium channel activity weakly potentiated. In normotensive Wistar rats, the increase of T-type calcium channel openings was greater than that of SHRsp. However, the effect of MCYST-LR appeared that only the increase of L-type calcium channel current in SHRsp was significant. It is suggested that the action of PKC and/or phosphorylation on the different components of calcium currents should be emphasized in the investigation of the mechanism in the increase in peripheral resistance during hypertension.