We studied the membrane effects of (1S,2S)-2-(2-[[3-2(benzimidazolyl) propyl]methylamino]ethyl)-6-fluoro-1, 2,3,4-tetrahydro-1-isopropyl-2-naphthyl-methoxyacetate dihydrochloride, Ro 40-5967, a new non-dihydropyridine (DHP) Ca2+ channel antagonist, on dog coronary and saphenous arterial vascular muscle cells using the whole-cell patch-clamp method. Long-lasting (L-type) inward currents in 20 mM Ba2+ were measured over a range of test potentials (300 ms) from -50 mV to +90 mV from a holding potential of -80 mV in the presence of 1 microM Bay k8644 (a DHP Ca2+ agonist). Ro 40-5967 caused a concentration-dependent suppression of Ca2+ channel currents in muscle cells from both arteries, with greater potency on coronary than saphenous arterial cells. The concentration of Ro 40-5967 which inhibited the magnitude of peak inward currents by 50% (IC50) was estimated to be 1 microM (n = 5) in muscle cells from coronary artery and 10 microM (n = 4) in saphenous artery. Ro 40-5967 (1 microM) decreased the amplitude of the activation current-voltage relationship for coronary L-type Ca2+ channel currents over a wider range of membrane potentials than verapamil, diltiazem, or nifedipine. In contrast, block of Ca2+ channel currents in saphenous artery cells by 1 microM Ro 40-5967 was only observed at command potentials positive to 0 mV. Ro 40-5967 (1 microM) significantly shifted the voltage-inactivation curve downward by 40% in coronary (n = 4), but only by 18% in saphenous arterial muscle cells (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)