Protein kinase‐C mediates dual modulation of L‐type Ca2+ channels in human vascular smooth muscle

FEBS Letters

Schuhmann, Klaus¹  Groschner, Klaus¹ 

[1] Institut für Pharmakologie und Toxikologie, Universität Graz, Universitätsplatz 2, Graz, Austria

关键词: L-type calcium channel;    Cellular regulation;    Phorbol ester;    Protein kinase C;    EGTA;    ethylene glycol bis (β-aminoethyl ether) N;    N;    N';    N'-tetraacetic acid;    H-7;    1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine;    HEPES;    N'-2-hydroxyethylpiperazine-N'-ethane-sulfonic acid;    P o;    channel's probability of being in the open state;    PKC;    protein kinase C;    PDD;    4-α-phorbol-12;    13-didecanoate;    TEA-C1;    tetraethyl-ammonium chloride;    TPA;    12-O-tetradecanoyl-phorbol-13-acetate;   

DOI  :  10.1016/0014-5793(94)80458-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 (TEA) 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-α-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.

【 授权许可】

Unknown