Chloride in smooth muscle

Abstract

Interest in the functions of intracellular chloride expanded about twenty years ago but mostly this referred to tissues other than smooth muscle. On the other hand, accumulation of chloride above equilibrium seems to have been recognised more readily in smooth muscle. Experimental data is used to show by calculation that the Donnan equilibrium cannot account for the chloride distribution in smooth muscle but it can in skeletal muscle. The evidence that chloride is normally above equilibrium in smooth muscle is discussed and comparisons are made with skeletal and cardiac muscle. The accent is on vascular smooth muscle and the mechanisms of accumulation and dissipation. The three mechanisms by which chloride can be accumulated are described with some emphasis on calculating the driving forces, where this is possible. The mechanisms are chloride/bicarbonate exchange, (Na+K+Cl) cotransport and a novel entity, "pump III", known only from own work. Their contributions to chloride accumulation vary and appear to be characteristic of individual smooth muscles. Thus, (Na+K+Cl) always drives chloride inwards, chloride/bicarbonate exchange is always present but does not always do it and "pump III" is not universal. Three quite different biophysical approaches to assessing chloride permeability are considered and the calculations underlying them are worked out fully. Comparisons with other tissues are made to illustrate that low chloride permeability is a feature of smooth muscle. Some of the functions of the high intracellular chloride concentrations are considered. This includes calculations to illustrate its depolarising influence on the membrane potential, a concept which, experience tells us, some people find confusing. The major topic is the role of chloride in the regulation of smooth muscle contractility. Whilst there is strong evidence that the opening of the calcium-dependent chloride channel leads to depolarisation, calcium entry and contraction in some smooth muscles, it appears that chloride serves a different function in others. Thus, although activation and inhibition of (Na+K+Cl) cotransport is associated with contraction and relaxation respectively, the converse association of inhibition and contraction has been seen. Nevertheless, inhibition of chloride/bicarbonate exchange and "pump III" and stimulation of (K+Cl) cotransport can all cause relaxation and this suggests that chloride is always involved in the contraction of smooth muscle. The evidence that (Na+K+Cl) cotransport more active in experimental hypertension is discussed. This is a common but not universal observation. The information comes almost exclusively from work on cultured cells, usually from rat aorta. Nevertheless, work on smooth muscle freshly isolated from hypertensive rats confirms that (Na+K+Cl) cotransport is activated in hypertension but there are several other differences, of which the depolarisation of the membrane potential may be the most important.Finally, a simple calculation is made which indicates as much as 40% of the energy...

Chloride/anion channels in glial cell membranes

“…These functions demonstrate that chloride is important in mechanisms of cell volume and pH control. It is now acknowledged that, in contrast to most other biological ions, chloride resting concentration shows significant variation among different mammalian cell types, as well as throughout the lifetime of some cell types (Cherubini et al, 1991;Chipperfield and Harper, 2000). The present review explores the role of chloride in glial function and correlates these concepts with new findings on cloned channels.…”

Hydrogen sulfide as an oxygen sensor

“…Chloride is accumulated against an electrochemical gradient by a variety of cells, including vascular smooth muscle, and it is an important regulator of vasoactivity (21,99). Metabolically generated bicarbonate (HCO 3 -) can interact with Cl -antiporters and produce either vasodilation or vasoconstriction (95,96).…”

The Cl− channel blocker niflumic acid releases Ca2+ from an intracellular store in rat pulmonary artery smooth muscle cells

“…It is widely accepted that this high intracellular Cl À concentration plays an important role in regulating a number of cellular functions, including intracellular pH, cell volume, contractility, and membrane potential (for a review see Chipperfield & Harper, 2000). Many of these cellular effects of Cl À are dependent upon the activities of Cl À channels.…”