Novel Pathways for Regulation of Sinoatrial Node Plasticity and Heart Rate

Abstract

Heart rate is an amazingly adaptive process with redundant pathways for both acute and chronic regulation in response to a wide range of environmental stimuli. Dramatic changes to basal heart rate are common not only in cardiovascular disease but also under physiological conditions (eg, exercise) as a way to match cardiac output with demand. Driving these changes in heart rate is alterations in activity of the sinoatrial node (SAN), a heterogeneous collection of specialized myocytes located in the right atrium. Defects in SAN function are increasingly common in an aging population (effects ≈1 in 600 patients over the age of 65 years) and manifest as prominent issues with heart rate control.1 Given the growing prevalence of SAN dysfunction and the limitations of available therapies, there is a great need to better understand the various ways the heart has evolved to control intrinsic rate. Article, see p 1058 Normal SAN function depends on a delicate balance between the activity of a relatively small number of automatic cells capable of spontaneously generating an action potential (AP) and the demands of surrounding atrial cells that require external stimulus for activation. This balance (and therefore heart rate) is readily tuned by perturbations at the cell and tissue level. SAN cell automaticity itself depends on a distinct ion channel expression profile that differs substantially from the ion channel signature present in atrial or ventricular cells.2 In contrast to ventricular and atrial cells, the SAN myocyte expresses virtually no inward rectifier K …