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 Ca2+ channel blocker d-cis- diltiazem, protects cardiac myocytes from ischemia and reperfusion injury i n the perfused heart and from veratridine-induced Ca2+ overload. We determi ned the effect of E-cis-diltiazem on the voltage-dependent Na+ current (I-N a) and lysophosphatidylcholine-induced currents in isolated guinea-pig left ventricular myocytes by a whole-cell patch-clamp technique. l-cis-Diltiaze m inhibited I-Na in a dose-dependent manner without altering the current-vo ltage relationship for I-Na (K-d values : 729 and 9 mu M at holding potenti als of -140 and -80 mV, respectively). A use-dependent block of I-Na, the l eftward shift of the steady-state inactivation curve and the delay of recov ery from inactivation suggest that l-cis-diltiazem has a higher affinity fo r the inactivated state of Na+ channels. In addition to I-Na, the lysophosp hatidylcholine-induced currents were inhibited by l-cis-diltiazem in a simi lar concentration range. It is suggested that inhibition of both Na+ channe ls and lysophosphatidylcholine-activated non-selective cation channels cont ributes to the cardioprotective effect of l-cis-diltiazem. (C) 2000 Elsevie r Science B.V. All rights reserved.