Desensitization of the acetylcholine-induced increase of potassium conductance in rabbit cardiac Purkinje fibres.

In rabbit cardiac Purkinje fibres, acetylcholine (ACh) changes membrane electrophysiological properties in a biphasic time course. On wash-out of ACh a rebound phenomenon is observed (Mubagwa & Carmeliet, 1983). The underlying mechanisms have been studied by the voltage-clamp technique. The ACh-induced increase in K+ current follows a biphasic time course during exposure to ACh. This time course is not due to intercellular accumulation or depletion of K+, but results from a desensitization process. On wash-out a rebound is obtained, i.e. the membrane K+ conductance transiently decreases below the control value. In contrast, the inhibition of ACh of the catecholamine-induced increase of slow inward current follows a monophasic time course. The desensitization process or secondary decrease of ACh-induced change in K+ current follows a mono- or a biexponential time course. The extent and rate of desensitization depend on ACh concentration. The rate of desensitization is not influenced by membrane potential but its extent seems to be increased by depolarization. Recovery from desensitization is relatively rapid and has a half-time of about 2 min. Different existing models for desensitization are discussed, no one of which accounts for all results in rabbit Purkinje fibres. Therefore, a three-state receptor model is proposed to explain the results. The model assumes that the K+ channel is directly associated with the muscarinic receptor and that the channel-receptor complex may be in closed, open or desensitized state, in the presence as well as in the absence of agonist.