Basal dephosphorylation controls slow gating of L‐type Ca2+ channels in human vascular smooth muscle

FEBS Letters

Schuhmann, Klaus²  Groschner, Klaus²  Schindler, Hansgeorg¹  Romanin, Christoph¹  Baumgartner, Werner¹  Pastushenko, Vassili¹ 

[1] Institut für Biophysik, Universität Linz, Linz, Austria;Institut für Pharmakologie und Toxikologie, Karl-Franzens-Universität Graz, Universitätsplatz 2, A-8010, Graz, Austria

关键词: L-type Ca2+ channel;    Protein phosphatase;    Cellular regulation;    Vascular smooth muscle;    Patch clamp;    EGTA;    ethylene glycol bis (β-aminoethyl ether) N;    N;    N′;    N′-tetraacetic acid;    H-7;    1-(5-isoquinolinylsulfonyl)-2-methylpiperazine;    HEPES;    N-2-hydroxyethylpiperazine-N′-ethansulfonic acid;    P0;    a channel's probability of being in the open state;    NP0;    mean number of open channels given by the product of N (number of active channels in a patch) times P0;   

DOI  :  10.1016/0014-5793(95)01012-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The role of cellular phosphatase activity in regulation of smooth muscle L-type Ca²⁺ channels was investigated using tautomycin, a potent and specific inhibitor of serin/threonin phosphatases type 1 and 2A. Tautomycin (1–100 nM) inhibited Ca²⁺ channel activity in smooth muscle cells isolated from human umbilical vein. Tautomycin-induced inhibition of Ca²⁺ channel activity was due to a reduction of channel availability which originated mainly from prolongation of the lifetime of unavailable states of the channel. Pretreatment of smooth muscle cells with the protein kinase inhibitor H-7 (10 μM) prevented the inhibitory effect of tautomycin. Our results suggest modulation of slow gating between available and unavailable states as a mechanism of phosphorylation-dependent down-regulation of Ca²⁺ channels in vascular smooth muscle.

【 授权许可】

Unknown