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

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.