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

Abstract

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 mM 6-hydroxydopamine (to functionally denervate the tissue), exogenous noradrenaline (5 nM) 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 mM to 42.5±2.2 mM (P<0.0001).

3. In the presence of 10 μM bumetanide (an inhibitor of (Na-K-Cl) cotransport), 5 nM noradrenaline caused a depolarization of E_m of 3.0±3.2 mV, and a rise in [Cl]_i of 4.5±2.5 mM.

4. In the presence of bumetanide and 1 mM 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 nM 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.

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