RECOVERY OF THE SLOW INWARD CURRENT FROM CA-2+-MEDIATED AND VOLTAGE-DEPENDENT INACTIVATION IN THE RABBIT SINOATRIAL NODE

The process of recovery from inactivation of the slow inward current (isi) in the rabbit sinoatrial (S-A) node was evaluated by voltage clamp experiments using double microelectrode method. Double pulse experiments were carried out on preparations loaded with Cs+ using nystatin. The rate of the rapid isi inactivation depended on the amplitude of isi rather than the membrane potential. After a 50 ms depolarizing prepulse, isi rapidly recovered from inactivation at -40 mV with a time constant of 84 ± 25 ms, whereas after a longer prepulse, an additional slow recovery phase with a time constant of 1 to 2 s was observed. The amount of isi during the fast recovery phase following a 300 ms prepulse to -20 mV was smaller than that following a prepulse to +20 mV, as predicted by a Ca2+-mediated inactivation mechanism. Conversely, a prepulse to +20 mV caused a greater inactivation in the slow recovery phase, suggesting a voltage-dependent mechanism. The inactivation curve obtained during the fast recovery phase using 50 ms prepulses was U-shaped, indicating a predominant role of the Ca2+-mediated mechanism, whereas that obtained during the slow recovery phase resembled previously reported voltage-dependent steady state inactivation (f∞) curve. These results indicate that the fast and slow phases of recovery reprenent the removal of Ca2+-mediated and voltage-dependent isi inactivation, respectively. The presence of Ca2+-mediated inactivation via steady state Ca2+ inflows was also suggested. © 1990.