&bgr;-Adrenergic Stimulation Modulates Ryanodine Receptor Ca2+Release During Diastolic Depolarization to Accelerate Pacemaker Activity in Rabbit Sinoatrial Nodal Cells
作者:
Tatiana Vinogradova,
Konstantin Bogdanov,
Edward Lakatta,
期刊:
Circulation Research: Journal of the American Heart Association
(OVID Available online 2002)
卷期:
Volume 90,
issue 1
页码: 73-79
ISSN:0009-7330
年代: 2002
出版商: OVID
关键词: sinoatrial node;&bgr;-adrenergic stimulation;ryanodine receptor;local Ca2+release
数据来源: OVID
摘要:
It has long been recognized that activation of sympathetic &bgr;-adrenoceptors (&bgr;-ARs) increases the spontaneous beating rate of sinoatrial nodal cells (SANCs); however, the specific links between stimulation of &bgr;-ARs and the resultant increase in firing rate remain an enigma. In the present study, we show that the positive chronotropic effect of &bgr;-AR stimulation is critically dependent on localized subsarcolemmal ryanodine receptor (RyR) Ca2+releases during diastolic depolarization (CRDD). Specifically, isoproterenol (ISO; 0.1 &mgr;mol/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/F0;P<0.05 [F and F0refer to peak and minimal fluorescence]); and an increase in spatial width (from 3.80±0.44 to 5.45±0.47 &mgr;m;P<0.05). The net effect results in an augmentation of the amplitude of the local preaction potential subsarcolemmal Ca2+transient that, in turn, accelerates the diastolic depolarization rate, leading to an increase in SANC firing rate. When RyRs are disabled by ryanodine, &bgr;-AR stimulation fails to amplify subsarcolemmal Ca2+releases, fails to augment the diastolic depolarization rate, and fails to increase the SANC firing rate, despite preserved &bgr;-AR stimulation-induced augmentation of L-type Ca2+current amplitude. Thus, the RyR Ca2+release acts as a switchboard to link &bgr;-AR stimulation to an increase in SANC firing rate: recruitment of additional localized CRDDs and partial synchronization of their occurrence by &bgr;-AR stimulation lead to an increase in the heart rate.
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