Calcium channel current facilitation in porcine adrenal chromaffin cells

The mechanisms of depolarizing-prepulse-induced facilitation of Ca2+ channel current were investigated in a study of porcine chromaffin cells. The Ba2+ current evoked by a pulse to 0 mV was increased by a strong depolarizing prepulse (conditioning pulse), termed "facilitation". This facilitation increased with an increase in either the duration or the voltage of the conditioning pulse, and decreased with an increase in the interpulse interval. For example, the Ba2+ current was increased to 1.14 times the control (facilitation ratio) by a 150-ms conditioning pulse to +100 mV followed by a 10-ms interpulse interval. Forskolin, 8-bromo-adenosine 3',5'-cyclic monophosphate (8-bromo-cAMP) and Rp-adenosine 3',5'-cyclic monophosphothioate (Rp-cAMPS) did not affect the facilitation of the Ba2+ current, suggesting that a cAMP-dependent mechanism is not involved. Intracellular guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) decreased the Ba2+ current to 0.59 times the control and GDP beta S increased it to 1.19. However, neither GTP gamma S nor guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) changed the amplitude of the Ba2+ current that was facilitated by the conditioning pulse. Thus, GTP gamma S increased the facilitation ratio to 2.05 and GDP beta S decreased it to 1.05. Furthermore, the facilitation of the Ba2+ current was abolished by omega-conotoxin GVIA but not by either omega-agatoxin IVA or nifedipine. These results suggest that, in porcine chromaffin cells, there is a omega-conotoxin GVIA-sensitive N-type Ca2+ channel that is under the inhibitory control of a G protein, which can be relieved by a conditioning pulse.