Key result
Acetylcholine at nanomolar concentrations slows spontaneous cardiac rate by inhibiting the hyperpolarization-activated current (If) rather than activating the acetylcholine-dependent potassium current.
At low concentrations, acetylcholine slows cardiac pacemaking primarily by inhibiting the hyperpolarization-activated current (If) rather than activating potassium channels.
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Questions canonical acetylcholine mechanism in pacemaking; leaves open translation to human sinoatrial node physiology.
Slowing of cardiac pacemaking induced by cholinergic input is thought to arise from the opening of potassium channels caused by muscarinic receptor stimulation. In mammalian sinoatrial node cells, however, muscarinic stimulation also inhibits the hyperpolarization-activated current ( I f ), which is involved in the generation of pacemaker activity and its acceleration by catecholamines. Acetylcholine at nanomolar concentrations inhibits I f and slows spontaneous rate, whereas 20 times higher concentrations are required to activate the acetylcholine-dependent potassium current ( I K,Ach ). Thus, modulation of I f , rather than I K,Ach , is the mechanism underlying the muscarinic control of cardiac pacing at low (nanomolar) acetylcholine concentrations.
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DiFrancesco et al. (1989) studied Cardiac pacemaking. Acetylcholine was evaluated on Inhibition of hyperpolarization-activated current (If) and spontaneous rate. Acetylcholine at nanomolar concentrations slows spontaneous cardiac rate by inhibiting the hyperpolarization-activated current (If) rather than activating the acetylcholine-dependent potassium current.
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