D-600 and the membrane stabilizing effect of calcium in vascular smooth muscle

Increases in the extracellular concentration of calcium diminish the rate of force development of vascular smooth muscle and cause relaxation of already contracted vascular smooth muscle. These actions of calcium are referred to as the 'membrane stabilizing effect' of the cation. The current study demonstrates that the calcium channel blocker, D-600, antagonizes the membrane stabilizing influence of calcium in isolated strips of rat tail artery. Contraction of the arterial strips was induced by application of methoxamine, KCl or caffeine. During the plateau phase of the methoxamine response, a stepwise increase in the concentration of calcium from 1.6 to 20.1 mM (2 mM increments) elicited dose-dependent decreases in the level of contraction (relaxation). Treatment with D-600 decreased the magnitude of contraction induced by methoxamine and inhibited relaxation in response to calcium. Similar results were observed when KCl was used to contract the arterial strips. The initial rate of force development in response to methoxamine was decreased by elevations in the extracellular concentration of calcium from 1.6 to 20.1 mM. D-600 antagonized this inhibitory effect of elevated calcium on the rate of force development. Contractile responses to caffeine were not altered by changes in the extracellular concentration of calcium nor by the addition of D-600 to the muscle bath. It is concluded that D-600 blocks the transmembrane movement of calcium and interferes with membrane sites which mediate the stabilizing effect of this cation.