ROLE OF INTRACELLULAR CALCIUM FOR NORADRENALINE-INDUCED DEPOLARIZATION IN RAT MESENTERIC SMALL ARTERIES

We have investigated the effect of intracellular calcium levels for me mbrane. potential during noradrenaline application in isolated small a rteries Rat mesenteric small arteries were mounted for isometric tensi on measurement. Smooth muscle membrane potentials were measured by con ventional intracellular electrodes, and intracellular calcium concentr ation was measured using Fura-2 fluorescence. Under control conditions , noradrenaline caused contraction and depolarization from -55.5 to -2 9.3 mV. In intact arteries, depleting intracellular calcium stores wit h thapsigargin caused smooth muscle hyperpolarization and inhibited co ntraction to noradrenaline. In de-endothelialized vessels, thapsigargi n still depleted calcium stores, but did not affect either the depolar ization or contraction caused by noradrenaline. In noradrenaline-activ ated vessels, inhibition of calcium influx by amlodipine caused tensio n and calcium levels to fall to near-baseline levels, but membrane pot ential returned by only 55%. Treatment with a combination of thapsigar gin, D-600 and BAPTA-AM inhibited the tension and calcium responses to noradrenaline, but the membrane potential response was reduced by onl y 34%. Acute reduction of extracellular chloride concentration caused similar, small depolarization at rest and during noradrenaline exposur e. It is concluded that an elevation of intracellular calcium concentr ation is not essential for noradrenaline depolarization, although part of the depolarization is associated with the raised intracellular cal cium level.