Intracellular cAMP potentiates voltage-dependent activation of L-type Ca2+ channels in rat islet β-cells

 Intracellular cAMP-dependent modulation of L-type Ca²⁺ channel activation in cultured rat islet β-cells has been investigated using the patch-clamp whole-cell current recording mode. The L-type voltage-dependent Ca²⁺ current (I _Ca) showed a fast activation followed by a slow inactivation, and was sensitive to Ca²⁺ channel blockers, for example nifedipine. Application of a cAMP analogue, dibutyryl cyclic AMP (db-cAMP), increased the magnitude of the peak I _Ca in a concentration-dependent manner. Values of the half-activation potentials (V _1/2), taken from activation curves for I _Ca, were –16.7 ± 1.8 and –21.9 ± 3.4 mV (P < 0.05) before and after application of db-cAMP, respectively, with no change of the slope factor (k) or the reversal potential. Pretreatment with a specific protein kinase A antagonist, Rp-cAMP, prevented the potentiating effect of db-cAMP. These results indicate that in rat islet β-cells, phosphorylation of cAMP-dependent kinase potentiates the voltage-dependent activation of L-type Ca²⁺ channels. Received: 9 September 1997 / Received after revision: 19 November 1997 / Accepted: 21 November 1997