INHIBITION OF SERINE/THREONINE PROTEIN PHOSPHATASES PROMOTES OPENING OF VOLTAGE-ACTIVATED L-TYPE CA2+ CHANNELS IN INSULIN-SECRETING CELLS

被引：41

作者：

HABY, C ^{[1
]}

LARSSON, O ^{[1
]}

ISLAM, MS ^{[1
]}

AUNIS, D ^{[1
]}

BERGGREN, PO ^{[1
]}

ZWILLER, J ^{[1
]}

机构：

[1] KAROLINSKA HOSP, KAROLINSKA INST, ROLF LUFT CTR DIABET RES, DEPT ENDOCRINOL, S-10401 STOCKHOLM, SWEDEN

来源：

BIOCHEMICAL JOURNAL | 1994年 / 298卷

关键词：

D O I：

10.1042/bj2980341

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The biological activity of many proteins, including voltage-sensitive ion channels, is controlled by their state of phosphorylation. Ca2+ influx through voltage-activated L-type Ca2+ channels serves as the major stimulatory signal in insulin-secreting cells. We have now investigated the extent to which Ca2+ handling in clonal insulin-secreting RiNm5F cells was affected by okadaic acid, an inhibitor of various serine/threonine protein phosphatases. Whole-cell patch-clamp experiments showed that okadaic acid generated an increase in membrane current, suggesting that it promotes Ca2+ influx through L-type voltage-gated Ca2+ channels probably by modifying their phosphorylation state. Okadaic acid was found to provoke a transient rise in the cytoplasmic free Ca2+ concentration ([Ca2+](i)), but had no further effect on the K+-induced increase. The Ca2+ transient induced by okadaic acid was dependent on the presence of extracellular Ca2+ and was abolished by D600, a blocker of voltage-activated L-type Ca2+ channels. Concomitant with the rise in [Ca2+](i), okadaic acid induced insulin secretion, a phenomenon that was also dependent on extracellular Ca2+. It is proposed that hyperphosphorylation of voltage-activated L-type Ca2+ channels in insulin-secreting cells lowers the threshold potential for their activation.

引用

页码：341 / 346

页数：6

共 23 条

[1]

ARKHAMMAR P, 1987, J BIOL CHEM, V262, P5448

[2] EXTRACELLULAR ATP INCREASES CYTOPLASMIC FREE CA-2+ CONCENTRATION IN CLONAL INSULIN-PRODUCING RINM5F CELLS - A MECHANISM INVOLVING DIRECT INTERACTION WITH BOTH RELEASE AND REFILLING OF THE INOSITOL 1,4,5-TRISPHOSPHATE-SENSITIVE CA-2+ POOL [J].