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 (Em) 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 Em 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 microM bumetanide (an inhibitor of (Na-K-Cl) cotransport), 5 nM noradrenaline caused a depolarization of Em 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 Em 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 ECl potentiating the depolarization caused by noradrenaline. The possibility that modulation of [Cl]i may be a general mechanism of Em regulation is discussed.
Davis
J P
JP
Department of Anatomy & Physiology, University of Dundee.
Harper
A A
AA
Chipperfield
A R
AR
D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D004232:Diuretics / Q000494:pharmacology; D005263:Femoral Artery; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D028021:Sodium-Potassium-Chloride Symporters
D002352:Carrier Proteins; D002712:Chlorides; D004232:Diuretics; D028021:Sodium-Potassium-Chloride Symporters; D002034:Bumetanide; D000086:Acetazolamide; D009638:Norepinephrine