Key result
Beta-adrenergic stimulation synchronizes sinoatrial node firing rate, with response strongly correlated to basal cycle length.
Why the study?
Although sinoatrial node cells represent a heterogeneous population, it was assumed that all cells increase action potential firing similarly during beta-adrenergic stimulation.
This study demonstrates that β-adrenergic stimulation synchronizes a heterogeneous population of SAN cells toward a higher average firing rate, challenging the dogma that all pacemaker cells uniformly increase their firing rates.
β-adrenergic stimulation synchronizes heterogeneous SAN cells to higher rates; leaves open translation to intact hearts or clinical sinus node function.
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 the heart rate commensurate with the cardiac output demand via stimulation of SAN β-adrenergic receptors (βAR). While SAN cells reportedly represent a highly heterogeneous cell population, the current dogma is that, in response to βAR stimulation, all cells increase their spontaneous AP firing rate in a similar fashion. The aim of the present study was to investigate the cell-to-cell variability in the responses of a large population of SAN cells. We measured the βAR responses among 166 single SAN cells isolated from 33 guinea pig hearts. In contrast to the current dogma, the SAN cell responses to βAR stimulation substantially varied. In each cell, changes in the AP cycle length were highly correlated (R2 = 0.97) with the AP cycle length before βAR 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 decreased their rate. Thus, βAR stimulation synchronized the operation of the SAN cell population toward a higher average rate, rather than uniformly shifting the rate in each cell, creating a new paradigm of βAR-driven fight-or-flight responses among individual pacemaker cells.
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Kim et al. (2021) studied Isolated Sinoatrial Node (SAN) Cells (n=166). Isoproterenol (β-adrenergic stimulation) vs. Basal state (before stimulation) was evaluated on Change in action potential (AP) cycle length. β-adrenergic stimulation synchronized SAN cell responses toward a higher average rate, with cycle length changes highly correlated (R2 = 0.97) to the basal AP cycle length.
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