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( 1/4 )), 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-cAM, 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.