Conductance and kinetics of delayed rectifier potassium channels in nodal cells of the rabbit heart.

Abstract

1. The delayed rectifier K+ current (IK) of single pace‐maker cells from the sino‐atrial node and the atrioventricular node of the rabbit heart was investigated using the whole‐cell and cell‐attached configurations of the patch‐clamp technique. 2. The activation kinetics of the macroscopic IK were not altered by varying the extracellular K+ concentration ([K+]o) between 5.4 and 150 mM. The amplitude of the tail current of IK, however, was about 10‐fold larger at a [K+]o of 150 mM than that at a [K+]o of 5.4 mM. 3. By using a high‐[K+]o solution, inward single‐channel currents were observed on repolarization from potentials positive to ‐40 mV. The current‐voltage (I‐V) relation was linear over the negative potential range and the reversal potential estimated by extrapolating the I‐V curve was shifted by about 60 mV for a 10‐fold increase in [K+]o, indicating that the channel was highly selective for K+. 4. The single‐channel conductance was 11.1 pS at a [K+]o of 150 mM and varied in proportion to the square root of [K+]o. The total number of channels was estimated as approximately 1000 per cell (0.7/micron 2). On repolarization, the averaged single‐channel current disappeared with a time constant similar to that of the macroscopic tail current of IK. 5. At potentials between ‐50 and ‐100 mV, the open and closed times of the single channel fitted well with single‐exponential and biexponential distributions, respectively. As the membrane was progressively depolarized, the open time was shortened while the closed time was prolonged, suggesting a decrease of open probability. These changes were in the opposite direction to those expected from the delayed rectifier K+ current which progressively increases in magnitude at more positive potentials. 6. At the beginning of the macroscopic tail current, a transient increase of the inward current was found to precede the time‐dependent decrease. This rapid initial change can be attributed to a quick removal of inactivation of IK which had occurred during the depolarizing pulse. This inactivation gate of the channel has very fast kinetics and could be responsible for the inward‐going rectification observed in the 'fully activated' IK.