INTRACELLULAR CAMP POTENTIATES VOLTAGE-DEPENDENT ACTIVATION OF L-TYPECA2-CELLS( CHANNELS IN RAT ISLET BETA)

Intracellular cAMP-dependent modulation of L-type Ca2+ channel activat ion in cultured rat islet beta-cells has been investigated using the p atch-clamp whole-cell current recording mode. The L-type voltage-depen dent Ca2+ current (I-Ca) showed a fast activation followed by a slow i nactivation, and was sensitive to Ca2+ channel blockers, for example n ifedipine. Application of a cAMP analogue, dibutyryl cyclic AMP (db-cA MP), increased the magnitude of the peak I-Ca in a concentration-depen dent manner. Values of the half-activation potentials (V-1/2), taken f rom activation curves for I-Ca, were -16.7 +/- 1.8 and -21.9 +/- 3.4 m V (P < 0.05) before and after application of db-cAMP, respectively, wi th no change of the slope factor (k) or the reversal potential. Pretre atment with a specific protein kinase A antagonist, Rp-cAMP, prevented the potentiating effect of db-cAMP. These results indicate that in ra t islet beta-cells, phosphorylation of cAMP-dependent kinase potentiat es the voltage-dependent activation of L-type Ca2+ channels.