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

A robust "fight or flight response", largely mediated via acute β-adrenergic receptor (β-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 β-AR increases the spontaneous beating rate of sinoatrial nodal cells (SANC), specific links between stimulation of β-ARs and the resultant increase in firing rate have not been evaluated. Our recent studies^1,2 employed imaging of subcellular Ca²⁺ release coupled with recording of membrane potential or current in single, isolated cardiac SANC, to seek novel links between β-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.