3 TYPES OF CA2+ CHANNEL TRIGGER SECRETION WITH DIFFERENT EFFICACIES IN CHROMAFFIN CELLS

To determine whether the different types of Ca2+ channels present in the same secretory cell contribute equally to secretion, we used chromaffin cells to analyse the coupling between three distinct types of Ca2+ channel1 and exocytosis2,3. These are omega-conotoxin-GVIA-sensitive4,5 N-type channels, omega-agatoxin-IVA-sensitive P-type Ca2+ channels6 and dihydropyridine-sensitive facilitation Ca2+ channels, which are normally quiescent but are activated by depolarizing pre-pulses, repetitive depolarizations to physiological potentials7,8, or agents that raise cyclic AMP9. We have simultaneously monitored changes in capacitance as an assay of catecholamine secretion10, and Ca2+ currents. Although all three types of Ca2+ channel trigger secretion individually, facilitation channels produce much greater secretion for a given size of Ca2+ current, indicating that they are coupled more efficiently to exocytosis. These results indicate that facilitation Ca2+ channels may be physically nearer vesicle release sites. They also show that low efficiency P- and N-type channels could trigger mild release and that high-efficiency facilitation channels may underlie the massive catecholamine release that occurs during the 'fight or flight' response.