PROTEIN-KINASE-C INHIBITS THE CA2+-ACTIVATED K+ CHANNEL OF CULTURED PORCINE CORONARY-ARTERY SMOOTH-MUSCLE CELLS
PROTEIN-KINASE-C INHIBITS THE CA2+-ACTIVATED K+ CHANNEL OF CULTURED PORCINE CORONARY-ARTERY SMOOTH-MUSCLE CELLS
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DOI：
10.1006/bbrc.1993.1040
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发表时间：
1993-01-15
影响因子：
3.1
通讯作者：
NAKAYA, Y
中科院分区：
文献类型：
--
作者：
MINAMI, K;FUKUZAWA, K;NAKAYA, Y
应用膜片钳技术研究了蛋白激酶C（C-激酶）对培养的猪冠状动脉平滑肌细胞钙激活钾通道（KCa-通道）的影响。在细胞贴附贴片中，在钙离子载体A23187（20 μM）存在下，浴用佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA，1 μM）（一种C-激酶激活剂）显著降低激活的KCa通道的开放概率，钙离子载体A23187可增加细胞内Ca 2+。这种开放概率的降低通过随后应用星形孢菌素（1 nM）（一种C-激酶抑制剂）逆转。应用C激酶激活剂1-油酰-2-乙酰甘油（OAG，30 μM）或1，2-二辛酰甘油（DG 8; 30 μM）也可抑制A23187对KCa通道的激活，并且这些抑制作用也可被星形孢菌素逆转。PMA（1 μM）也可抑制二丁基环磷酸腺苷（db-cAMP，2 mM）或咖啡因（30 mM）对KCa通道的激活。在由内而外的贴片中，在ATP（1 mM）和PMA（1 μM）存在下，浴用来自大鼠脑的C-激酶组分显著抑制KCa通道。这些结果表明，激活C-激酶抑制KCa-通道，并可能导致膜去极化和血管收缩。
The effect of protein kinase C (C-kinase) on the Ca2+-activated K+channel (KCa-channel) was studied in cultured smooth muscle cells from porcine coronary artery by the patch-clamp technique. In cell-attached patches, bath application of phorbol 12-myristate 13-acetate (PMA, 1 μM), a C-kinase activator, significantly decreased the open probability of the activated KCa-channel in the presence of the calcium ionophore A23187 (20 μM), which increases intracellular Ca2+. This decrease in the open probability was reversed by subsequent application of staurosporine (1 nM), a C-kinase inhibitor. Application of 1-oleoyl-2-acetylglycerol (OAG, 30 μM) or 1,2-dioctanoylglycerol (DG8; 30 μM), activators of C-kinase, also inhibited KCa-channel activation by A23187, and these inhibitions were also reversed by staurosporine. PMA (1 μM) also inhibited KCa-channel activation by dibutylyl cyclic AMP (db-cAMP, 2 mM) or caffeine (30 mM). In inside-out patches, bath application of the C-kinase fraction from rat brain in the presence of ATP (1 mM) and PMA (1 μM ) markedly inhibited the KCa-channel. These results indicate that activation of C-kinase inhibits the KCa-channel and may cause membrane depolarization and vascular contraction.