Stimulation of intracellular chloride accumulation by noradrenaline and hence potentiation of its depolarization of rat arterial smooth muscle in vitro

1 Double‐barrelled ion‐selective microelectrodes were used to examine the effects of exogenous noradrenaline upon the membrane potential (E m ) and intracellular chloride concentration ([Cl] i ) of arterial smooth muscle from the saphenous branch of the femoral artery of the rat. 2 After treatment with 0.6 m M  6‐hydroxydopamine (to functionally denervate the tissue), exogenous noradrenaline (5 n M ) caused repeatable depolarization of E m from −63.7±2.4 mV (s.d., n =18) to −53.8±3.4 mV ( P <0.0001) and increases in [Cl] i from 31.0±0.5 m M to 42.5±2.2 m M ( P <0.0001). 3 In the presence of 10 μ M bumetanide (an inhibitor of (Na‐K‐Cl) cotransport), 5 n M noradrenaline caused a depolarization of E m of 3.0±3.2 mV, and a rise in [Cl] i of 4.5±2.5 m M . 4 In the presence of bumetanide and 1 m M acetazolamide (used as an inhibitor of a Na‐independent inward Cl pump), noradrenaline had no effect on E m or [Cl] i . 5 In the absence of extracellular chloride, the rise in apparent [Cl] i in response to 5 n M noradrenaline was abolished but there was a depolarization of 2.0±3.9 mV. 6 These results are consistent with the stimulation of (Na‐K‐Cl) cotransport and a Na‐independent Cl pump by exogenous noradrenaline and with the consequent increase in [Cl] i and shift in E Cl potentiating the depolarization caused by noradrenaline. The possibility that modulation of [Cl] i may be a general mechanism of E m regulation is discussed.British Journal of Pharmacology (1997) 122 , 639–642; doi: 10.1038/sj.bjp.0701431