Modulation of L-type Ca²⁺ channel currents by various protein kinase activators and inhibitors in rat clonal pituitary GH₃ cell line

L-type Ca²⁺ channels play an important role in regulating cytosolic Ca²⁺ and thereby regulating hormone secretions in neuroendocrine cells. Since hormone secretions are also regulated by various kinds of protein kinases, we investigated the role of some kinase activators and inhibitors in the regulation of the L-type Ca²⁺ channel currents in rat pituitary GH₃ cells using the patch-clamp technique. Phorbol 12,13-dibutyrate (PDBu), a protein kinase C (PKC) activator, and vanadate, a protein tyrosine phosphatase (PTP) inhibitor, increased the Ba²⁺ current through the L-type Ca²⁺ channels. In contrast, bisindolylmaleimide I (BIM I), a PKC inhibitor, and genistein, a protein tyrosine kinase (PTK) inhibitor, suppressed the Ba²⁺ currents. Forskolin, an adenylate cyclase activator, and isobutyl methylxanthine (IBMX), a non-specific phosphodiesterase inhibitor, reduced Ba²⁺ currents. The above results show that the L-type Ca²⁺ channels are activated by PKC and PTK, and inhibited by elevation of cyclic nucleotides such as cAMP. From these results, it is suggested that the regulation of hormone secretion by various kinase activity in GH₃ cells may be attributable, at least in part, to their effect on L-type Ca²⁺ channels.