Properties of adenosine‐triphosphate‐regulated potassium channels in guinea‐pig ventricular cells.

Abstract

A class of K channels in cardiac muscle is reversibly blocked by intracellular ATP. The characteristics of this K channel were studied by recording single-channel currents in ventricular cells isolated enzymatically from guinea-pig heart. The reversal potential of single-channel currents agreed well with the K equilibrium potential. Blockers of other K channels, such as tetraethylammonium and 4-aminopyridine, decreased the mean open time of the channel. The chord conductance increased as the 0.24th power of the K concentration on the outer surface of the membrane, and showed a marked inward-going rectification on strong depolarization. The degree of rectification was larger with increasing Na concentration on the inner side of the membrane. The kinetics of the channel were almost voltage independent, but depended on the concentration of intracellular ATP. The conductance of the channel was not affected by ATP. When channel kinetics were examined in the presence of ATP, the distribution of open times and closed times was fitted well with a sum of 2 exponential components. When ATP concentration was increased, the time constants obtained from the open-time histogram decreased and those from the closed-time histogram increased, resulting in a decrease of the open-state probability. The channel was blocked by ATP, ADP,5''-adenylylimidodiphosphate, GTP and UTP, but not by AMP, creatine phosphate, creatine or adenosine. Plots of the open-state probability vs. the ATP concentration revealed by Michaelis-Menten saturation kinetics with strong co-operating of multiple receptor sites (Hill coefficient 3-4, concentration of half-saturation 0.5 mM). This K channel has 3 or 4 receptor sites selective for triphosphate nucleotide on the inner surface of the membrane, and that the channel is blocked through the binding of agonists to the receptors.