Modulation of noradrenaline‐induced membrane currents by papaverine in rabbit vascular smooth muscle cells.

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Abstract
1. The modulation of noradrenaline‐induced membrane currents by papaverine was studied with the nystatin whole‐cell technique in freshly isolated rabbit ear artery and portal vein cells. 2. At a holding potential of ‐50 mV (in potassium‐free conditions), papaverine inhibited the Ca(2+)‐activated inward chloride current ICl(Ca) evoked by ionophoretic application of noradrenaline in rabbit portal vein cells in a concentration‐dependent (10(‐5)‐10(‐4) M) manner. 3. With potassium‐containing solutions (at 0 mV) 10(‐4) M‐papaverine reversibly abolished the Ca(2+)‐activated outward potassium current IK(Ca) induced by noradrenaline in both protal vein and ear artery cells. Occasionally, 10(‐4) M‐papaverine itself activated IK(Ca) before it abolished the response to noradrenaline. 4. Higher concentrations of papaverine (up to 10(‐3) M) always evoked both ICl(Ca) and IK(Ca) at ‐50 and 0 mV respectively, before it abolished these responses to noradrenaline in both ear artery and portal vein cells. In the presence of 10(‐3) M‐papaverine higher doses of noradrenaline evoked the non‐selective cation current in some portal vein cells. 5. In the presence of 10(‐2) M‐caffeine, which elicited both IK(Ca) and ICl(Ca), papaverine (10(‐3) M) failed to activate either current and 10(‐3) M‐papaverine reduced the caffeine‐induced IK(Ca) by 94%. In contrast, IK(Ca) induced by the calcium ionophore ionomycin was unaffected by papaverine. In Ca(2+)‐free, 1 mM‐EGTA external solutions, 10(‐3) M‐papaverine still induced IK(Ca) and blocked the response to noradrenaline. 6. The alpha 1‐adrenoceptor antagonist prazosin (5 x 10(‐8) M) completely blocked the noradrenaline‐induced IK(Ca) but currents evoked by papaverine (10(‐3) M) were unaffected by prazosin. 7. It was concluded that papaverine modulated noradrenaline‐induced membrane currents in vascular smooth muscle cells by releasing and depleting caffeine‐sensitive intracellular Ca2+ stores.