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

• Published in: British journal of pharmacology Vol. 122; no. 4; pp. 639 - 642
• Main Authors: Davis, Julian P. L., Harper, Alexander A., Chipperfield, Alan R.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-10-1997; Nature Publishing
• Subjects: (Na‐K‐Cl) cotransport; acetazolamide; Acetazolamide - pharmacology; Animals; arterial smooth muscle; Biological and medical sciences; Blood vessels and receptors; bumetanide; Bumetanide - pharmacology; Carrier Proteins - antagonists & inhibitors; Carrier Proteins - metabolism; Chlorides - metabolism; Diuretics - pharmacology; Femoral Artery; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; intracellular chloride; Male; membrane potential; Membrane Potentials - drug effects; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - physiology; Noradrenaline; Norepinephrine - pharmacology; Rats; Rats, Sprague-Dawley; Sodium-Potassium-Chloride Symporters; Vertebrates: cardiovascular system; Femoral artery; Rat; Electrophysiology; Smooth muscle; Ionic current; K; Neuromodulation; Mechanism; Depolarization; Regulation(control); Na; Chlorides; Blood vessel; Membrane potential; Enzyme; Rodentia; Catecholamine; Muscle contraction; In vitro; Vertebrata; Mammalia; Animal; Neurotransmitter; Hydrolases; exchanging ATPase; Norepinephrine; Circulatory system; Intracellular
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0701431

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 μM 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.
British Journal of Pharmacology (1997) 122, 639–642; doi:10.1038/sj.bjp.0701431