Funny channels in the control of cardiac rhythm and mode of action of selective blockers
Abstract
"Funny" (f) channels underlie the cardiac "pacemaker"I(f) current, originally described as an inward current activated on hyperpolarization to the diastolic range of voltages in sino-atrial node myocytes [Brown, HF, DiFrancesco, D, Noble, SJ. How does adrenaline accelerate the heart? Nature 1979;280:235-236]. The involvement of funny channels in the generation and modulation of cardiac pacemaker activity has been amply demonstrated by thorough analysis since its discovery. The degree of funny current activation upon termination of an action potential determines the slope of diastolic depolarization, and hence pacemaker frequency; furthermore, I(f) is under cAMP-mediated control by beta-adrenergic and muscarinic stimulation and underlies the modulation of cardiac rate by the autonomous nervous system: it therefore represents a mechanism of fundamental physiological relevance. Their function in pacemaking makes funny channels an obvious target for drugs aiming at regulation of spontaneous activity and cardiac rate. This explains the recent development of "heart rate-reducing" drugs which act as selective f-channel inhibitors, and as such are capable of specifically slow cardiac frequency by decreasing the rate of diastolic depola...Continue Reading
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