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

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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

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Okadaic Acid
Phosphoprotein Phosphatases
Insulin-Secreting Cells
Insulin
Electric potential
Phosphorylation
Gallopamil
Clamping devices
Bioactivity
Ion Channels
Chemical activation
Membranes
Proteins
Experiments

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.

Inhibition of serine/threonine protein phosphatases promotes opening of voltage-activated L-type Ca2+ channels in insulin-secreting cells. / Haby, C.; Larsson, O.; Islam Md., S.; Aunis, D.; Berggren, P. O.; Zwiller, J.

In: Biochemical Journal, Vol. 298, No. 2, 18.03.1994, p. 341-346.

Research output: Contribution to journalArticle

Haby, C, Larsson, O, Islam Md., S, Aunis, D, Berggren, PO & Zwiller, J 1994, 'Inhibition of serine/threonine protein phosphatases promotes opening of voltage-activated L-type Ca2+ channels in insulin-secreting cells', Biochemical Journal, vol. 298, no. 2, pp. 341-346.
Haby, C. ; Larsson, O. ; Islam Md., S. ; Aunis, D. ; Berggren, P. O. ; Zwiller, J. / Inhibition of serine/threonine protein phosphatases promotes opening of voltage-activated L-type Ca2+ channels in insulin-secreting cells. In: Biochemical Journal. 1994 ; Vol. 298, No. 2. pp. 341-346.
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