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).
Zilberter
Y u
Yu
Institute of General Pathology and Pathological Physiology, Moscow, USSR.
Motin
L
L
Sokolova
S
S
Papin
A
A
Khodorov
B
B
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004553:Electric Conductivity; D007700:Kinetics; D008012:Lidocaine / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*
D015222:Sodium Channels; D008012:Lidocaine; D002118:Calcium