beta-Adrenergic stimulation modulates ryanodine receptor Ca(2+) release during diastolic depolarization to accelerate pacemaker activity in rabbit sinoatrial nodal cells - PubMed (original) (raw)
. 2002 Jan 11;90(1):73-9.
doi: 10.1161/hh0102.102271.
Affiliations
- PMID: 11786521
- DOI: 10.1161/hh0102.102271
beta-Adrenergic stimulation modulates ryanodine receptor Ca(2+) release during diastolic depolarization to accelerate pacemaker activity in rabbit sinoatrial nodal cells
Tatiana M Vinogradova et al. Circ Res. 2002.
Abstract
It has long been recognized that activation of sympathetic beta-adrenoceptors (beta-ARs) increases the spontaneous beating rate of sinoatrial nodal cells (SANCs); however, the specific links between stimulation of beta-ARs and the resultant increase in firing rate remain an enigma. In the present study, we show that the positive chronotropic effect of beta-AR stimulation is critically dependent on localized subsarcolemmal ryanodine receptor (RyR) Ca(2+) releases during diastolic depolarization (CRDD). Specifically, isoproterenol (ISO; 0.1 micromol/L) induces a 3-fold increase in the number of CRDDs per cycle; a shift to higher CRDD amplitudes (from 2.00+/-0.04 to 2.17+/-0.03 F/F(0); P<0.05 [F and F(0) refer to peak and minimal fluorescence]); and an increase in spatial width (from 3.80+/-0.44 to 5.45+/-0.47 microm; P<0.05). The net effect results in an augmentation of the amplitude of the local preaction potential subsarcolemmal Ca(2+) transient that, in turn, accelerates the diastolic depolarization rate, leading to an increase in SANC firing rate. When RyRs are disabled by ryanodine, beta-AR stimulation fails to amplify subsarcolemmal Ca(2+) releases, fails to augment the diastolic depolarization rate, and fails to increase the SANC firing rate, despite preserved beta-AR stimulation-induced augmentation of L-type Ca(2+) current amplitude. Thus, the RyR Ca(2+) release acts as a switchboard to link beta-AR stimulation to an increase in SANC firing rate: recruitment of additional localized CRDDs and partial synchronization of their occurrence by beta-AR stimulation lead to an increase in the heart rate.
Comment in
- Calcium and cardiac rhythms: physiological and pathophysiological.
Bers DM. Bers DM. Circ Res. 2002 Jan 11;90(1):14-7. Circ Res. 2002. PMID: 11786512 No abstract available. - Sarcoplasmic reticulum Ca2+ release is not a dominating factor in sinoatrial node pacemaker activity.
Honjo H, Inada S, Lancaster MK, Yamamoto M, Niwa R, Jones SA, Shibata N, Mitsui K, Horiuchi T, Kamiya K, Kodama I, Boyett MR. Honjo H, et al. Circ Res. 2003 Feb 21;92(3):e41-4. doi: 10.1161/01.res.0000055904.21974.be. Circ Res. 2003. PMID: 12595347
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