Enhanced Ca2+-induced Ca2+ release from intracellular stores contributes to catecholamine hypersecretion in adrenal chromaffin cells from spontaneously hypertensive rats

摘要

Adrenal chromaffin cells (CCs) from spontaneously hypertensive rats (SHRs) secrete more catecholamine (CA) upon stimulation than CCs from normotensive Wistar Kyoto rats (WKY). Unitary CA exocytosis events, both spontaneous and stimulated, were amperometrically recorded from cultured WKY and SHR CCs. Both strains display spontaneous amperometric spikes but SHR CCs produce more spikes and of higher mean amplitude. After a brief stimulation with high K+ or caffeine which produces voltage-gated Ca2+ influx or intracellular Ca2+ release, respectively, more spikes and of greater mean amplitude and unitary charge were recorded in SHR CCs. Consequently, peak cumulative charge was similar to 2-fold higher in SHR CCs. Ryanodine (10 mu M), a specific blocker of the ryanodine receptors reduced depolarization-induced peak cumulative charge by similar to 10 % in WKY and similar to 77 % in SHR CCs, suggesting, a larger contribution of Ca2+-induced Ca2+ release to CA exocytosis in SHR CCs. Accordingly, Ca2+ imaging showed larger [Ca2+](i) signals induced both by depolarization and caffeine in SHR CCs. Distribution amplitude histograms showed that small amperometric spikes (0-50 pA) are more frequent in WKY than in SHR CCs. Conversely, medium (50-190 pA) and large (190-290 pA) spikes are more numerous in SHR than in WKY CCs. This study reveals that the enhanced CA secretion in SHR CCs results from a combination of (1) larger depolarization-induced Ca2+ transients, due to a greater Ca2+-induced intracellular Ca2+ release, (2) more exocytosis events per time unit, and (3) a greater proportion of medium and large amperometric spikes probably due to a higher mean CA content per granule. Enhanced CA release by excessive amplification by Ca2+ induced Ca2+ release and larger granule catecholamine content contributes to the increased CA plasma levels and vasomotor tone in SHRs.