D 600 block of L-type Ca2+ channel in vascular smooth muscle cells: comparison with permanently charged derivative, D 890.

It has been reported that D 600 blocks the high-threshold Ca2+ channel (L-type) from the outside in isolated vascular and ileal smooth muscle cells of the rabbit (Y. Ohya, K. Terada, K. Kitamura, and H. Kuriyama. Pfluegers Arch. 408: 80-82, 1987). We have reinvestigated this hypothesis by comparing the effects of external and internal applications of D 600 and the permanently charged quaternary derivative D 890 on the whole cell Ca2+ current (Ica) recorded in vascular smooth muscle cells isolated from the rabbit portal vein. At low frequencies of stimulation (0.05 Hz), externally applied D 600 inhibited Ica in a dose-dependent fashion, with a complete block occurring at 10(-4) M. D 600 was approximately 1,000 times more potent than D 890 for causing inhibition of Ica using this protocol. During a train of stimulations at 0.5 Hz, D 600 (10(-6) M) produced a minor additional frequency-dependent block of Ica, as shown in other preparations. During superfusion with D 890 (10(-4) M), a similar protocol produced little if any decline in the amplitude of Ica. No evidence of block could be detected during intracellular dialysis of D 600 (10(-4) M). At the same concentration, intracellular application of D 890 produced a slow block of Ica. To test whether D 600 could be effectively dialysed using a patch micropipette, similar experiments were performed in cardiac ventricular myocytes. In this preparation, intracellular dialysis of D 600 induced a rapid inhibition of the Ica.(ABSTRACT TRUNCATED AT 250 WORDS)