R-type Ca2+ channels are coupled to the rapid component of secretion in mouse adrenal slice chromaffin cells

Patch-clamp measurements of Ca2+ currents and membrane capacitance were per formed on slices of mouse adrenal glands, using the perforated-patch config uration of the patch-clamp technique. These recording conditions are much c loser to the in vivo situation than those used so far in most electrophysio logical studies in adrenal chromaffin cells (isolated cells maintained in c ulture and whole-cell configuration). We observed profound discrepancies in the quantities of Ca2+ channel subtypes (P-, Q-, N-, and L- type Ca2+ chan nels) described for isolated mouse chromaffin cells maintained in culture. Differences with respect to previous studies may be attributable not only t o culture conditions, but also to the patch-clamp configuration used. Our e xperiments revealed the presence of a Ca2+ channel subtype never before des cribed in chromaffin cells, a toxin and dihydropyridine-resistant Ca2+ chan nel with fast inactivation kinetics, similar to the R-type Ca2+ channel des cribed in neurons. This channel contributes 22% to the total Ca2+ current a nd controls 55% of the rapid secretory response evoked by short depolarizin g pulses. Our results indicate that R-type Ca2+ channels are in close proxi mity with the exocytotic machinery to rapidly regulate the secretory proces s.