Gap junctions mediate electrical signaling and ensuing cytosolic Ca2+ increases between chromaffin cells in adrenal slices: A role in catecholamine release

In adrenal chromaffin cells, a rise in cytosolic calcium concentration ([ C a2+]i) is a key event in the triggering of catecholamine exocytosis after s planchnic nerve activation. Action potential-or nicotine-induced [Ca2+]i tr ansients are well described in individual chromaffin cells, but whether the y remain spatially confined to the stimulated cell or propagate to adjacent cells is not yet known. To address this issue, the spatiotemporal organiza tion of electrical and associated Ca2+ events between chromaffin cells was investigated using the patch-clamp technique and real-time confocal imaging in rat acute adrenal slices. Spontaneous or electrically evoked action pot ential-driven [Ca2+]i transients were simultaneously detected in neighborin g cells. This was likely attributable to gap junction-mediated electrotonic communication, as shown by (1) the bidirectional reflection of voltage cha nges monitored between cell pairs, (2) Lucifer yellow (LY) diffusion betwee n cells exhibiting spontaneous synchronized [Ca2+]i transients, and (3) the reduction of LY diffusion using the uncoupling agent carbenoxolone. Furthe rmore, transcripts encoding two connexins (Cx36 and Cx43) were found in sin gle chromaffin cells. This gap junctional coupling was activated after a sy naptic-like application of nicotine that mediated synchronous multicellular [Ca2+]i increases. In addition, nicotinic stimulation of a single cell tri ggered catecholamine release in coupled cells, as shown by amperometric det ection of secretory events. Functional coupling between chromaffin cells in situ may represent an efficient complement to synaptic transmission to amp lify catecholamine release after synaptic stimulation of a single excited c hromaffin cell.