Comparison of the electrophysiological effect of amiodarone, lidocaine and quinidine on rat ventricular cells.
The effects of 20 microM each of amiodarone, lidocaine and quinidine on action potential and membrane currents were studied in rat ventricular cells. At a stimulation frequency of 0.1 Hz, quinidine prolonged the action potential duration (APD50) from 120 +/- 26 to 660 +/- 8 msec and increased the time to peak (Tp) amplitude from 7 +/- 1 msec to 32 +/- 6 msec. Lidocaine shortened APD50 from 123 +/- 15 to 83 +/- 6 msec without altering Tp. Amiodarone changed neither APD50 nor Tp. Voltage clamp study revealed that quinidine inhibited sodium inward current (INa) even when this current was elicited by depolarizing pulses at 0.1 Hz from a holding potential of -90 mV. For amiodarone and lidocaine, the inhibition was observed when INa was elicited from a holding potential of -70 mV. A frequency-dependent inhibition of INa by amiodarone and lidocaine was observed at frequencies higher than 1 Hz. Quinidine showed this inhibition even at 1 Hz. In correlation with the stronger frequency dependent inhibition of INa, a greater delay of the recovery and increase of the non-recovery fraction of INa was induced by quinidine. For lidocaine and amiodarone, only the recovery time constant was delayed. In cells treated with sea anemone toxin (ATX, 0.2 microM), APD50 was prolonged to 4-5 sec in 5 min. Quinidine, but not amiodarone, completely reversed the effect of ATX. Quinidine showed use-dependent inhibition of INa in these ATX-treated cells. Amiodarone, however, did not show this inhibition. It is likely that amiodarone suppresses INa by delaying the recovery of INa instead of blocking the open-state Na(+)-channels.(ABSTRACT TRUNCATED AT 250 WORDS)
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, R.O.C.
M J
MJ
Su
S O
SO
Lin
C H
CH
Wang
Y Z
YZ
Tseng
C D
CD
Tseng
D000200:Action Potentials / Q000187:drug effects; D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003064:Cnidarian Venoms / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects; D008012:Lidocaine / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011802:Quinidine / Q000494:pharmacology*; D051381:Rats; D012964:Sodium / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects*
D003064:Cnidarian Venoms; D007473:Ion Channels; D008012:Lidocaine; D012964:Sodium; D011802:Quinidine; D000638:Amiodarone; D011188:Potassium; D002118:Calcium