Membrane Potential and Calcium Channels in Arterial Smooth Muscle Cells

Abstract

Noradrenaline and membrane depolarization decrease the diameters of arteries. We found that noradrenaline and membrane depolarization can contract rabbit mesenteric arteries by a common mechanism, namely by opening voltage-dependent calcium channels. The effects of noradrenaline and membrane depolarization on calcium channels were examined directly at the single channel level using the patch clamp technique. Membrane depolarization increased calcium entry by elevating the open state probability (Po) approximately 2.7 fold for an 8 mV depolarization over the physiological range of membrane potentials. Noradrenaline also increased Po in the absence of a membrane depolarization. The effect of noradrenaline may be mediated by a second messenger, because it exerts its influence without directly contacting the channels. These results predict that steady state contractions to noradrenaline would depend on calcium entry through voltage-dependent calcium channels. Indeed, noradrenaline contractions increased with membrane depolarization or with the calcium channel agonist, Bay R 5417, and were inhibited by organic and inorganic calcium channel blockers. In all cases, maintained contractions increased about 2.7 fold for an 8 mV depolarization, suggesting that the voltage-dependence of calcium channels was responsible for this voltage-dependence. Therefore, in the presence of noradrenaline, calcium channels can open over the physiological range of membrane potentials. These results suggest that any agent that changes membrane potential can affect force and blood vessel diameter.