β-Adrenergic Stimulation Synchronizes a Broad Spectrum of Action Potential Firing Rates of Cardiac Pacemaker Cells towards a Higher Population Average

Abstract

The heartbeat is initiated by pacemaker cells residing in the sinoatrial node (SAN). SAN cells generate spontaneous action potentials (APs), i.e. normal automaticity. The sympathetic nervous system increases heart rate commensurate with blood supply and cardiac output demand, known as the fight-or-flight response, via stimulation of SAN β-adrenergic receptors (βAR). It is classically believed that all cells increase their spontaneous AP firing rate in a similar fashion. In the present study we measured βAR responses among 166 single SAN cells isolated from 33 guinea pig hearts. However, the responses substantially varied. In each cell changes in AP cycle length in response to βAR stimulation highly correlated (R2=0.97) with the AP cycle lengths before stimulation. While, as expected, on average the cells increased their pacemaker rate, greater responses were observed in cells with slower basal rates, and vice versa, cells with higher basal rates showed smaller responses, no responses, or even negative responses, i.e. their rate decreased. Thus, βAR stimulation synchronizes operation of the cell population towards a higher average rate, rather than uniformly shifting the rate in each cell, creating a new paradigm of fight-or-flight response among individual pacemaker SAN cells.