Bidirectional flow of the funny current (I <sub>f</sub> ) during the pacemaking cycle in murine sinoatrial node myocytes
Colin H. Peters, Pin W. Liu, Stefano Morotti, Stephanie C. Gantz, Eleonora Grandi, Bruce P. Bean, Catherine Proenza
Abstract
Significance The funny current (I f ) is critical for spontaneous activity in cardiac pacemaker cells; however, its precise role remains enigmatic because it activates mostly outside the physiological voltage range and its kinetics are slow relative to the cardiac cycle. I f is typically considered as an inward current; however, we show that I f is persistently active in pacemaker cells. Once opened, the small fraction of ion channels that conduct I f do not reclose. Consequently, I f flows both inward and outward and, paradoxically, conducts a large fraction of the net charge movement. These results establish a new conceptual framework for pacemaking in which voltage-dependent gating of I f is minimal and I f contributes to spontaneous pacemaker activity by providing driving force in both directions.