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

Abstract

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 Ca(2+) influx or intracellular Ca(2+) release, respectively, more spikes and of greater mean amplitude and unitary charge were recorded in SHR CCs. Consequently, peak cumulative charge was ~2-fold higher in SHR CCs. Ryanodine (10 μM), a specific blocker of the ryanodine receptors reduced depolarization-induced peak cumulative charge by ~10 % in WKY and ~77 % in SHR CCs, suggesting, a larger contribution of Ca(2+)-induced Ca(2+) release to CA exocytosis in SHR CCs. Accordingly, Ca(2+) imaging showed larger [Ca(2+)]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 Ca(2+) transients, due to a greater Ca(2+)-induced intracellular Ca(2+) 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 Ca(2+) induced Ca(2+) release and larger granule catecholamine content contributes to the increased CA plasma levels and vasomotor tone in SHRs.

Effects of reversible SERCA inhibition on catecholamine exocytosis and intracellular [Ca2+] signaling in chromaffin cells from normotensive Wistar Kyoto rats and Spontaneously Hypertensive rats

“…Figures 1A and 1B are representative amperometric recordings obtained from a WKY and an SHR CC in response to depolarizing stimuli. As reported earlier, SHR CCs produced more secretory events than WKY CCs after each stimulation [34]. Also, the kinetic parameters of the amperometric spikes showed noticeable inter-strain differences (see Figs.…”

“…In CCs with two Ca 2+ components, simultaneous amperometry also shows two bursts of exocytosis. The late Ca 2+ transient component is abolished with CPA and Ryanodine, suggesting that it represents the contribution of CICR.Previously, we reported that membrane depolarization triggered [Ca 2+ ]c elevations and catecholamine secretion ~ 3 fold greater in CCs from SHRs than age-matched WKY rats CCs[34], and that ryanodine, a RyRs blocker, caused a drastic reduction (77%) in amperometric cumulative charge, mainly due to a 71% decrease in the number of spikes[34], demonstrating that CICR contribution to catecholamine hypersecretion in SHR CCs is linked to stronger intracellular Ca 2+ signals. Possible explanations for the enhanced gain of CICR in SHR CCs include excessive RyRs expression, greater Ca 2+ content of the SER, and increased Ca 2+ sensitivity of the RyRs.Since ryanodine speci cally suppressed CA hypersecretion in SHR CCs, it could be hypothesized that agents that inhibit RyR function could attenuate hypertension development in this animal model.…”

“…5). The depolarization-induced [Ca 2+ ]c increase is 3-fold greater in SHR CCs than in WKY CCs [34]. Incubation with the ryanodine receptor blocker ryanodine (10 µM) diminished the depolarization-induced CA secretion by 77% in SHR CCs and only 10% in WKY CCs, demonstrating that RyRs-mediated intracellular…”

“…Ca 2+ release has a more signi cant contribution in SHR CCs to CA exocytosis [34]. Nonetheless, the impact of RyR-mediated CICR on the intracellular Ca 2+ signaling in rat CCs from these two strains had not been examined before.…”

Protective effects of calorie restriction and 17-β estradiol on cardiac hypertrophy in ovariectomized obese rats

“…The animal tail was placed in contact with a cuff, and a pulse transducer was used to measure the systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and mean arterial pressure (MAP). An average of 4 pressure readings was recorded for each measurement [ 35 ].…”