Schuhmann K, Groschner K
Institut für Pharmakologie und Toxikologie, Universität Graz, Austria.
FEBS Lett. 1994 Mar 21;341(2-3):208-12. doi: 10.1016/0014-5793(94)80458-3.
The role of protein kinase C (PKC) in cellular regulation of L-type Ca2+ channels was investigated in human umbilical vein smooth muscle. Activation of PKC, by low concentrations (< 30 nM) of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) caused inhibition of Ca2+ channels, while higher concentrations of TPA (> 100 nM) elicited a transient rise, followed by sustained inhibition of Ca2+ channel activity in cell-attached patches. Low TPA concentrations predominantly reduced channel availability, while high concentrations of TPA (100 nM) transiently increased channel availability and, in addition, prolonged mean open time. The inactive 4-alpha-phorbol-12,13- didecanoate failed to affect channel activity, and pretreatment of the cells with PKC inhibitors (H-7, chelerythrine) antagonized inhibitory and stimulatory effects of TPA. Our results provide evidence for two distinct PKC-dependent mechanisms of L-type Ca2+ channel regulation in smooth muscle.
在人脐静脉平滑肌中研究了蛋白激酶C（PKC）在细胞对L型钙通道调节中的作用。低浓度（<30 nM）的12-O-十四烷酰佛波醇-13-乙酸酯（TPA）激活PKC会导致钙通道受到抑制，而较高浓度的TPA（>100 nM）会引起短暂升高，随后在细胞贴附式膜片中钙通道活性持续受到抑制。低浓度TPA主要降低通道的可利用性，而高浓度TPA（100 nM）会短暂增加通道可利用性，此外还会延长平均开放时间。无活性的4-α-佛波醇-12,13-十二酸酯不会影响通道活性，用PKC抑制剂（H-7、白屈菜红碱）对细胞进行预处理可拮抗TPA的抑制和刺激作用。我们的结果为平滑肌中L型钙通道调节的两种不同的PKC依赖性机制提供了证据。
