Key result
The funny current (If) is persistently active in murine pacemaker cells, flowing both inward and outward to conduct a large fraction of the net charge movement during the pacemaking cycle.
Why the study?
The precise role of the funny current in cardiac pacemaker cells remains enigmatic because it activates mostly outside the physiological voltage range and exhibits kinetics that are slow relative to the cardiac cycle.
Refines murine pacemaker models; leaves open translation to human rhythm disorders.
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.
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Peters et al. (2021) studied this question. Funny current (If) was evaluated on Role of funny current in pacemaking cycle. The funny current (If) is persistently active in murine pacemaker cells, flowing both inward and outward to conduct a large fraction of the net charge movement during the pacemaking cycle.
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