Ca-sensitive slow inactivation and lidocaine-induced block of sodium channels in rat cardiac cells.

Macroscopic and single Na channel currents were studied using the patch-clamp technique in rat cardiac cells. Slow inactivation (SI) characterized by 100 ms order kinetics was investigated. This inactivation was incomplete, as no more than 50% of Na channels were able to enter the SI state during 1-2 s of membrane depolarization. The maximal fraction of Na channels in the SI state decreased with increasing external Ca concentration. Single-channel analysis led us to conclude that Na channels undergo transition from the resting (R) state to the SI state, bypassing both open (O) and ordinary fast inactivation (I) states. A new fast inactivation state (Y) was postulated between the R and SI states. Exposure to the local anesthetic, lidocaine, decreased the probability of Na channel opening and dramatically slowed reactivation. The latter effect was due to lidocaine interaction with the Y state rather than the I state. Increasing external Ca concentration in the presence of lidocaine diminished the fraction of Na channels capable of making the transition to a slowly reactivatable state (lidocaine-bound Y and/or SI states).