Inwardly rectifying single-channel and whole cell K+ currents in rat ventricular myocytes

Abstract

The voltage-dependent properties of inwardly rectifying potassium channels were studied in adult and neonatal rat ventricular myocytes using patch voltage-clamp techniques. Inward rectification was pronounced in the single-channel current-voltage relation and outward currents were not detected at potentials positive to the calculated reversal potential for potassium (EK). Single-channel currents having at least three different conductances were observed and the middle one was predominant. Its single-channel conductance was nonlinear ranging from 20 to 40 pS. Its open-time distribution was fit by a single exponential and the time constants decreased markedly with hyperpolarization from EK. The distribution of the closed times required at least two exponentials for fitting, and their taus were related to the bursting behavior displayed at negative potentials. The steady-state probability of being open (P0) for this channel was determined from the single-channel records; in symmetrical isotonic K solutions P0 was 0.73 at -60 mV, but fell to 0.18 at -100 mV. The smaller conductance was about one-half the usual value and the open times were greatly prolonged. The large conductance was about 50 percent greater than the usual value and the open times were very brief. The P0(V) relation, the kinetics and the conductance of the predominant channel account for most of the whole cell inwardly rectifying current. The kinetics suggest that an intrinsic K+-dependent mechanism may control the gating, and the conductance of this channel. In the steady state, the opening and closing probabilities for the two smaller channels were not independent of each other, suggesting the possibility of a sub-conductance state or cooperativity between different channels.