Time- and voltage-dependent block of the delayed K+ current by quinidine in rabbit sinoatrial and atrioventricular nodes

Abstract

The modes in which quinidine blocks the delayed K+ current (IK) of rabbit sinoatrial and atrioventricular nodes were investigated by voltage clamp experiments using small preparations. Depolarizing pulses were applied from a holding potential of -50 mV and resultant IK current was evaluated. At a concentration of 2 x 10(-6) M, quinidine blocked 52 +/- 5% of IK with a 1000-msec test pulse of 0 mV, whereas it inhibited the slow inward current by only 5 to 10%. IK inhibition was enhanced with increasingly larger depolarizations. The activation curve obtained with the use of 1000-msec test pulses shifted toward hyperpolarization by 3.0 mV and its slope factor increased from 7.3 to 8.8, suggesting a voltage-dependent mechanism for IK blockage. Short and small depolarizing pulses from the holding potential of -50 mV hardly affected II. The activation of IK in the presence of quinidine did not show any delay. These results indicated a low affinity of quinidine to the closed (deactivated) channels. The deactivation time constant of IK was significantly prolonged from 120 to 145 msec at -50 mV. By applying the modulated receptor model to the K+ current, the tail current in the presence of quinidine was well reconstructed when the time constant of drug-channel interactions was 300 msec at -50 mV and 2000 msec at -30 mV. It is suggested that the unblocking of quinidine slows the decay of the IK tail current.