Abstract 17405: Small K+ Channel Activity Modulates Sinoatrial Node Pacemaker Rate and Explains the Abnormal Bursts of Sinoatrial Node Pacing in Atrial-Specific Na+/Ca2+ Exchange Knockout Mice

Rationale: Ca2+-sensitive small K+ (SK) channels have been implicated in abnormal atrial repolarization, automaticity and conduction in the heart. Despite their potential role in sinoatrial node (SAN) dysfunction, their presence and contribution to SAN pacemaker activity are unknown. Objective: To prove SK expression in murine SAN, and to investigate their ability to translate diastolic Ca2+ variation into membrane voltage changes during normal and pro-arrhythmic SAN automaticity. Methods and results: Immunostaining, quantitative-PCR and patch clamp recordings demonstrated functional presence of all SK isoforms (SK1, SK2 and SK3) in the SAN. Since SK channels are exquisitely sensitive to Ca2+ changes, we compared their activity in control mice and in a mouse model of SAN cell diastolic Ca2+ overload, resulting from atrial-specific ablation of the Na+/Ca2+ exchanger (NCX KO). Wildtype (WT) littermates were used as control (equal ratio M/F). In WT SAN cells, induced and spontaneous action potentials (APs), ...