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Protein kinase‐C mediates dual modulation of L‐type Ca 2+ channels in human vascular smooth muscle
Author(s) -
Schuhmann Klaus,
Groschner Klaus
Publication year - 1994
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(94)80458-3
Subject(s) - protein kinase c , chelerythrine , phorbol , tetradecanoylphorbol acetate , umbilical vein , vascular smooth muscle , chemistry , biophysics , protein kinase a , microbiology and biotechnology , endocrinology , smooth muscle , medicine , biochemistry , signal transduction , kinase , biology , in vitro
The role of protein kinase C (PKC) in cellular regulation of L‐type Ca 2+ 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 Ca 2+ channels, while higher concentrations of TPA (>100 nM) elicited a transient rise, followed by sustained inhibition of Ca 2+ 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 Ca 2+ channel regulation in smooth muscle.