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Review
. 1998 Jun 1;509 ( Pt 2)(Pt 2):315-25.
doi: 10.1111/j.1469-7793.1998.315bn.x.

Hypoxia and smooth muscle function: key regulatory events during metabolic stress

M J Taggart  1 , S Wray
Affiliations
Review

Hypoxia and smooth muscle function: key regulatory events during metabolic stress

M J Taggart et al. J Physiol. .

Abstract

Hypoxia rapidly reduces force in many smooth muscles and we review recent data that shed light on the mechanisms involved. As many regulated cellular processes are integrated to co-ordinate smooth muscle contractility, the processes responsible for decreased force output with altered metabolism are also likely to be many, acting in concert, rather than the actions of one altered parameter. Nevertheless the aim of this study is to elucidate the hierarchical series of events that contribute to reduced smooth muscle force production during altered metabolism. We conclude that in many phasic smooth muscles the decrease in force can be attributed to impaired electro-mechanical coupling whereby the Ca2+ transient is reduced. A direct effect of hypoxia on the Ca2+ channel may be of key importance. In tonic vascular smooth muscles KATP channels may also play a role in the integrated functional responses to hypoxia. There are also many examples of force being reduced, in tonically activated preparations, without a fall in steady-state Ca2+; indeed it usually increases. We examine the roles of altered [ATP], pH, myosin phosphorylation, inorganic phosphate and proteolytic activity on the [Ca2+]-force relationship during hypoxia. We find no defining force-inhibitory role for any one factor acting alone, and suggest that force most probably falls as a result of the combination of myriad factors.

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Figures

Figure 1
Figure 1. Simultaneous force (top) and intracellular [Ca2+] (bottom) measurements before, during and after cyanide application to guinea-pig ureter
A, phasic contractions produced by action potentials following electrical stimulation. B, tonic contraction produced by high K+ depolarization. The Ca2+ measurements were made from the ratio of the fluorescence signals of indo-1 emitted at 400 and 500 nm. Adapted from Bullock & Wray, 1998.
Figure 3
Figure 3. Changes in uterine force and myosin phosphorylation with cyanide
A, simultaneous force (top) and Ca2+ (bottom) records showing the effect of hypoxia on a depolarized rat uterine preparation. Note the increased Ca2+ record in hypoxia, but the fall of force. B, MLC phosphorylation measurements during contraction for 10 min produced by high K+, in the presence and absence of hypoxia. There was no significant difference in the amount of MLC phosphorylation at any time point; mean data from densiotometric scans of silver stained 2-D gels (see inset). U, unphosphorylated; P, phosphorylated. Figure adapted from Taggart et al. 1997.
Figure 2
Figure 2. A scheme to show the possible mechanism underlying the fall of phasic contractions in hypoxia
Hypoxia reduces O2, pH and ATP, and increases Ca2+, Mg2+ and ADP. These changes affect the opening of Ca2+ channels, which underly the Ca2+ transient.
See this image and copyright information in PMC

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