Modulation of L-type Ca<SUP>2&#8290;</SUP> Channel Currents by Various Protein Kinase Activators and Inhibitors in Rat Clonal Pituitary GH<SUB>3</SUB> Cell Line

Modulation of L-type Ca<SUP>2&#8290;</SUP> Channel Currents by Various Protein Kinase Activators and Inhibitors in Rat Clonal Pituitary GH<SUB>3</SUB> Cell Line

<P> L-type Ca<SUP>2&#8290;</SUP> channels play an important role in regulating cytosolic Ca<SUP>2&#8290;</SUP> 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 Ca<SUP>2&#8290;</SUP> channel currents in rat pituitary GH<SUB>3</SUB> 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 Ba<SUP>2&#8290;</SUP> current through the L-type Ca<SUP>2&#8290;</SUP> channels. In contrast, bisindolylmaleimide I (BIM I), a PKC inhibitor, and genistein, a protein tyrosine kinase (PTK) inhibitor, suppressed the Ba<SUP>2&#8290;</SUP> currents. Forskolin, an adenylate cyclase activator, and isobutyl methylxanthine (IBMX), a non-specific phosphodiesterase inhibitor, reduced Ba<SUP>2&#8290;</SUP> currents. The above results show that the L-type Ca<SUP>2&#8290;</SUP> 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 GH<SUB>3</SUB> cells may be attributable, at least in part, to their effect on L-type Ca<SUP>2&#8290;</SUP> channels.