We studied the effect of protein kinase C (PKC) inhibition and activation on voltage-dependent Ca2+ channels in rat insulinoma RINm5F cells. PKC down-regulation by chronic (24 h) treatment with the PKC activator phorbol 12-myristate 13-acetate (PMA) reduced by about 60% the Ba2+ currents through L- and non-L, non-N-type high-voltage-activated Ca2+ channels, indicating that PKC tonically up-regulates the two main Ca2+ channel subtypes of RINm5F cells under basal conditions. Consistently, PKC activation by acute PMA application caused only a modest increase (average 23%) of Ba2+ currents in a minority of cells (24%). L- and non-L, non-N-type channels were differentially up-regulated by either basal or stimulated PKC activation. Acute up-regulation was predominant on L-type channels and caused an I/V shift of the Ba2+ currents in the hyperpolarizing direction. Non-L, non-N-type channels were less affected by acute PMA application, possibly reflecting a more effective tonic PKC up-regulatory action. Unexpectedly, the increase of Ba2+ currents during acute PMA application was followed by a progressive current decrease, which was also observed in isolation in another 24% of the cells and could be ascribed to PKC-induced ATP depletion, rather than to a direct effect of PKC on Ca2+ channels. We also provide evidence that PKC-mediated phosphorylation is not involved in the G-protein-mediated noradrenergic modulation of Ca2+ channels in RINm5F cells.

Up-regulation of L- and non-L, non-N-type Ca2+ channels by basal and stimulated protein kinase C activation in insulin-secreting RINm5F cells

POLLO, Antonella;CARBONE, Emilio;
1996-01-01

Abstract

We studied the effect of protein kinase C (PKC) inhibition and activation on voltage-dependent Ca2+ channels in rat insulinoma RINm5F cells. PKC down-regulation by chronic (24 h) treatment with the PKC activator phorbol 12-myristate 13-acetate (PMA) reduced by about 60% the Ba2+ currents through L- and non-L, non-N-type high-voltage-activated Ca2+ channels, indicating that PKC tonically up-regulates the two main Ca2+ channel subtypes of RINm5F cells under basal conditions. Consistently, PKC activation by acute PMA application caused only a modest increase (average 23%) of Ba2+ currents in a minority of cells (24%). L- and non-L, non-N-type channels were differentially up-regulated by either basal or stimulated PKC activation. Acute up-regulation was predominant on L-type channels and caused an I/V shift of the Ba2+ currents in the hyperpolarizing direction. Non-L, non-N-type channels were less affected by acute PMA application, possibly reflecting a more effective tonic PKC up-regulatory action. Unexpectedly, the increase of Ba2+ currents during acute PMA application was followed by a progressive current decrease, which was also observed in isolation in another 24% of the cells and could be ascribed to PKC-induced ATP depletion, rather than to a direct effect of PKC on Ca2+ channels. We also provide evidence that PKC-mediated phosphorylation is not involved in the G-protein-mediated noradrenergic modulation of Ca2+ channels in RINm5F cells.
1996
391(1-2)
189
194
RINm5F; insulinoma; canali del calcio di tipo L e non-L; PKC; G protein; modulazione noradrenergica
Platano D; Pollo A; Carbone E; Aicardi G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/110862
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