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. 1987 Nov;392:617–635. doi: 10.1113/jphysiol.1987.sp016800

Regulation of cell calcium and contractility in mammalian arterial smooth muscle: the role of sodium-calcium exchange.

T Ashida 1, M P Blaustein 1
PMCID: PMC1192324  PMID: 2451733

Abstract

1. The contraction and relaxation of rings of rat thoracic aorta and bovine tail artery were examined as a function of changes in the Na+ electrochemical gradient in order to determine the role of Na-Ca exchange in the control of contractility. 2. Inhibition of the Na+ pump in rat aorta by K+-free media or a low concentration (5 x 10(-5) M) of strophanthidin reversibly increased the contractile responses to caffeine and noradrenaline. These effects were dependent upon external Ca2+ and were observed even in the presence of a Ca2+ channel blocker (10 microM-verapamil or 10 microM-diltiazem) and an alpha-receptor blocker (10 microM-phentolamine). 3. Reduction of external Na+ concentration, [Na+]o (replaced by N-methylglucamine, tetramethylammonium or Tris), also caused an external Ca2+-dependent increase in tonic tension and, in rat aorta, an increase in the response to caffeine. These effects were also observed in the presence of verapamil and phentolamine. 4. Caffeine relaxed the bovine tail artery, but increased the sensitivity of the rat aorta to reduced [Na+]o. The latter effect was presumably due to block of Ca2+ sequestration in the sarcoplasmic reticulum, so that entering Ca2+ was more effective in raising the intracellular free Ca2+ level, [Ca2+]i. 5. Relaxation from K+-free or low-Na+ contractions, in Ca2+-free media, depended upon [Na+]o. Reduction of [Na+]o to 1.2 or 7.5 mM slowed the relaxation of rat aorta (5 mM-caffeine present) 3- to 5-fold, and the relaxation of bovine tail artery (without caffeine) 5- to 10-fold. These effects were seen in the presence of verapamil and phentolamine. 6. These observations are all consistent with an Na-Ca exchange transport system that can move Ca2+ either into or out of the arterial smooth muscle cells. Ca2+ entry is enhanced by raising [Na+]i (by Na+ pump inhibition) and/or lowering [Na+]o. Ca2+ extrusion from the contracted muscles is largely dependent upon external Na+. The latter observation implies that, when [Ca2+] exceeds the contraction threshold, Ca2+ efflux is mediated primarily by the Na-Ca exchanger, rather than by the sarcolemmal ATP-driven Ca2+ pump. 7. When bovine tail artery was treated with verapamil and phentolamine, and [Na+]o was reduced from 139.2 to 43.9 mM, substitution of K+ for Na+ induced a larger external Ca2+-dependent contraction than did substitution of Tris for Na+. The amplitudes of these contractions were greatly increased when the Na+ pump was inhibited by 5 x 10(-5) M-strophanthidin, presumably because of the rise in [Na+]i.(ABSTRACT TRUNCATED AT 400 WORDS)

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Selected References

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