Inhibition of serine/threonine protein phosphatases promotes opening of voltage-activated L-type Ca2+ channels in insulin-secreting cells

C. Haby, O. Larsson, S. Islam Md., D. Aunis, P. O. Berggren, J. Zwiller

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)341-346
Number of pages6
JournalBiochemical Journal
Volume298
Issue number2
StatePublished - Mar 18 1994
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry

Cite this

Haby, C., Larsson, O., Islam Md., S., Aunis, D., Berggren, P. O., & Zwiller, J. (1994). Inhibition of serine/threonine protein phosphatases promotes opening of voltage-activated L-type Ca2+ channels in insulin-secreting cells. Biochemical Journal, 298(2), 341-346.