The Role of Mg2+ in the Modulation of IRK3 by M1 Acetylcholine Receptor

Abstract

Near the resting membrane potential, there are inward rectifier potassium channels (IRK) that are active. The biophysical hallmark of IRK channels is their ability to pass more inward than outward current, giving them their name. Because IRK channels are blocked by intracellular cations including Mgt+ or polyamines at the membrane potential above the equilibrium potential of potassium ions (EK) (Fakler et al. 1995; Ficker et al. 1994; Lopatin et al. 1994; Matsuda 1991; Matsuda et al. 1987; Stanfield et al. 1994; Vandenberg 1987), gating of inward rectifier K+ channels shifts with the extracellular potassium concentration. In most excitable cells, the resting membrane potential is higher than EK. Under this circumstance, IRK channels pass only outward current. When the inward current elicited by an excitatory input is large enough to overcome the outward current through IRK channels, membrane depolarization takes place. This depolarization will potentiate the voltage-dependent block of IRK channels by intracellular cations and reduce their ability to maintain the membrane potential close to the resting level, and will finally allow the firing of an action potential. The regulation of IRK channels, therefore, influences the membrane excitability.