Potassium channels and the muscarinic receptor in the sino-atrial node of the heart

Abstract

Vagal stimulation or application of acetylcholine (ACh) slows the spontaneous activity of the sinus node, the pacemaker of the mammalian heart, and eventually arrests the heart. A potential-sensing electrode in a cell of the sinus node sees a decrease in the rate of diastolic depolarisation which results in a longer diastolic period. At stronger stimulation the membrane hyperpolarises, an effect which was first observed in the tortoise heart by Gaskell (1886). Burgen and Terroux (1953) studied the hyperpolarisation in response to carbachol application in cat atria and found it to depend on the extracellular potassium concentration being smaller at higher concentrations. They suggested an increase in the potassium permeability as the inhibitory mechanism in the heart. The increase in the potassium permeability could directly be shown as an increase in the ⁴²K efflux on application of acetylcholine to the frog and turtle sinus venosus and auricles (Harris and Hutter, 1956). Also, in constant current experiments on mammalian atrial muscle, a reversal potential could be demonstrated at which on application of ACh the hyperpolarisation turned into a depolarising response. The reversal potential depended on the extracellular potassium concentration in a way expected for a potassium electrode (Trautwein and Dudel, 1958).