Biological Heart Rate Reduction Through Genetic Suppression of Gα s Protein in the Sinoatrial Node

Abstract

Elevated heart rate represents an independent risk factor for cardiovascular outcome in patients with heart disease. In the sinoatrial node, rate increase is mediated by β(1) adrenoceptor mediated activation of the Gα(s) pathway. We hypothesized that genetic inactivation of the stimulatory Gα(s) protein in the sinoatrial node would provide sinus rate control and would prevent inappropriate heart rate acceleration during β-adrenergic activation.