Beta-adrenergic stimulation modulation of heart rate via synchronization of ryanodine receptor Ca2+ release

A robust "fight or flight response", largely mediated via acute beta-adrenergic receptor (beta-AR) stimulation to the heart to increase its beating rate and contractile performance, is an essential component of the vertebrate survival instinct. While it has long been recognized that activation of beta-AR increases the spontaneous beating rate of sinoatrial nodal cells (SANC), specific links between stimulation of beta-ARs and the resultant increase in firing rate have not been evaluated. Our recent studies employed imaging of subcellular Ca2+ release coupled with recording of membrane potential or current in single, isolated cardiac SANC, to seek novel links between beta-AR stimulation and ryanodine receptor Ca2+ release and heart rate. An overview of these recent results, which provides novel insights into mechanisms of cardiac reserve that underlie the "fight or flight instinct, is presented here.