Electrophysiological effect of l-cis-diltiazem, the stereoisomer of d-cis-diltiazem, on isolated guinea-pig left ventricular myocytes.
l-cis-Diltiazem, the stereoisomer of the L-type Ca(2+) channel blocker d-cis-diltiazem, protects cardiac myocytes from ischemia and reperfusion injury in the perfused heart and from veratridine-induced Ca(2+) overload. We determined the effect of l-cis-diltiazem on the voltage-dependent Na(+) current (I(Na)) and lysophosphatidylcholine-induced currents in isolated guinea-pig left ventricular myocytes by a whole-cell patch-clamp technique. l-cis-Diltiazem inhibited I(Na) in a dose-dependent manner without altering the current-voltage relationship for I(Na) (K(d) values : 729 and 9 microM at holding potentials of -140 and -80 mV, respectively). A use-dependent block of I(Na), the leftward shift of the steady-state inactivation curve and the delay of recovery from inactivation suggest that l-cis-diltiazem has a higher affinity for the inactivated state of Na(+) channels. In addition to I(Na), the lysophosphatidylcholine-induced currents were inhibited by l-cis-diltiazem in a similar concentration range. It is suggested that inhibition of both Na(+) channels and lysophosphatidylcholine-activated non-selective cation channels contributes to the cardioprotective effect of l-cis-diltiazem.
Hashimoto
Y
Y
Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., 2-2-50, Kawagishi, Toda, Saitama, Japan. y-hashi@tanabe.co.jp
Yabana
H
H
Murata
S
S
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000737:chemistry / Q000494:pharmacology*; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000502:physiology; D013237:Stereoisomerism
D002121:Calcium Channel Blockers; D008244:Lysophosphatidylcholines; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D004110:Diltiazem