A rate theory model for Mg2+ block of ATP-dependent potassium channels of rat skeletal muscle

1. We have studied the block by intracellular Mg2+ (0.08-4 mM) of ATP-dependent potassium channels (K-ATP channels) from rat skeletal muscle using inside-out excised sarcolemmal patches. The block is voltage dependent, is relieved by extracellular potassium and has rapid kinetics, allowing the use of amplitude distribution analysis to estimate on and off rates. 2. To gain insight into the pore properties necessary to produce such a block, we have used an energy barrier model based on Eyring rate theory The model has two energy wells and three barriers for K+ within the pore, while intracellular Mg2+ has access only to the inner well. We fitted the model to unitary current-voltage relations in different [Mg2+], to on and off rates, and to dissociation constants for Mg2+ block. 3. The voltage dependence of block was almost entirely due to the rate constant for unblocking. This implies that the inner energy barrier is asymmetrical, so that Mg2+ entry senses little of the voltage field, but Mg2+ exit senses about 20% of the voltage field. Best fits were obtained by placing the barrier and binding site 0.01 and 0.22, respectively, of the electrical distance through the pore from the inside. 4. The relief of block by [K+](o) resulted from an increase in the unblocking rate for Mg2+, implying ionic repulsion between ions in the pore.