Visceral smooth muscle cells (VSMC) play an essential role, through changes in their contraction-relaxation cycle, in the maintenance of homeostasis in biological systems. The features of these cells differ markedly by tissue and by species; moreover, there are often regional differences within a given tissue. The biophysical features used to investigate ion channels in VSMC have progressed from the original extracellular recording methods (large electrode, single or double sucrose gap methods), to the intracellular (microelectrode) recording method, and then to methods for recording from membrane fractions (patch-clamp, including cell-attached patch-clamp, methods). Remarkable advances are now being made thanks to the application of these more modern biophysical procedures and to the development of techniques in molecular biology. Even so, we still have much to learn about the physiological features of these channels and about their contribution to the activity of both cell and tissue. In this review, we take a detailed look at ion channels in VSMC and at receptor-operated ion channels in particular; we look at their interaction with the contraction-relaxation cycle in individual VSMC and especially at the way in which their activity is related to Ca2+ movements and Ca2+ homeostasis in the cell. In sections II and III, we discuss research findings mainly derived from the use of the microelectrode, although we also introduce work done using the patch-clamp procedure. These sections cover work on the electrical activity of VSMC membranes (sect. II) and on neuromuscular transmission (sect. III). In sections IV and V, we discuss work done, using the patch-clamp procedure, on individual ion channels (Na+, Ca2+, K+, and Cl-; sect. IV) and on various types of receptor-operated ion channels (with or without coupled GTP-binding proteins and voltage dependent and independent; sect. V). In sect. VI, we look at work done on the role of Ca2+ in VSMC using the patch-clamp procedure, biochemical procedures, measurements of Ca2+ transients, and Ca2+ sensitivity of contractile proteins of VSMC. We discuss the way in which Ca2+ mobilization occurs after membrane activation (Ca2+ influx and efflux through the surface membrane, Ca2+ release from and uptake into the sarcoplasmic reticulum, and dynamic changes in Ca2+ within the cytosol). In this article, we make only limited reference to vascular smooth muscle research, since we reviewed the features of ion channels in vascular tissues only recently.
1. The excitation—contraction coupling mechanism in the smooth muscle of the guinea‐pig mesenteric artery was studied using intact and chemically skinned muscle cells. 2. The mean membrane potential of the intact smooth muscle was ‐65.8 ± 2.4 mV. It was electrically quiescent. Caffeine (5 m m), procaine (> 1 m m) and TEA (> 1 m m) depolarized the membrane, increased the membrane resistance and in their presence, outward current pulses evoked action potentials with overshoot. These potential changes were still observed in Na‐deficient solution but were abolished in the presence of 3 m m‐MnCl2. 3. Caffeine (5 m m) and TEA (1 m m) produced contractions in the intact muscle which were suppressed by procaine (5‐10 m m). Caffeine (5 m m) continued to produce contraction even after prolonged exposure to Ca‐free solution (containing 2 m m‐EGTA) and this contraction was suppressed by procaine (5 m m). On the other hand, the K‐induced contraction was rapidly abolished in 0‐Ca. 4. Electrical stimulation (1 sec) in the presence of TTX (10−7 m) evoked a contraction. Caffeine (5 m m) and TEA (5 m m) enhanced but procaine (5 m m) suppressed the contraction. 5. Chemically skinned smooth muscle cells were prepared by adding saponin, 50 μg/ml., to the relaxing solution. The minimum concentration of free Ca required to evoke contraction in skinned muscle cells was 1‐2 × 10−7 m and the maximum contraction was produced at 10−5 m. When Ca was replaced with Sr, the above relationship also shifted to the right (ED50 for Ca is 4.4 × 10−7 m and that for Sr is 1.5 × 10−5 m). Treatment with high concentrations of caffeine and procaine had no effect on the pCa—tension relationship. 6. Caffeine induced contraction in skinned muscle cells preloaded with Ca, and this contraction was markedly suppressed by procaine (5‐10 m m). 7. In skinned muscles, depolarization of the internal membrane by replacement of K with choline (116 m m) in the relaxing solution produced contraction, but the amplitude was much smaller than the caffeine‐induced contraction. 8. The relationship between the amplitude of caffeine‐induced contraction and the duration of preincubation in various Ca concentrations was observed in skinned muscles. The minimum concentration of Ca required to produce a subsequent caffeine‐induced contraction was itself below threshold for contraction. The results also indicate that the Ca‐induced Ca release mechanism appears to modify the amount of Ca stored by preincubation in over 3 × 10−7 m free Ca. 9. When the amount of Ca stored in intact cells was estimated from the caffeine‐induced contraction evoked in Ca‐free solution following preincubation with Ca, Ca applied simultaneously with procaine increased and Ca with caffeine reduced the Ca stored in the cell. After preincubation in 2.5 m m‐[Ca]o with 1 m m‐procaine for 5 min, the amplitude of the subsequently generated caffeine‐induced contraction (5 m m) in Ca‐free solution (2 min) was much the same as that observed in 118 m m‐[K]o. 10. The results support the view that the excitation—contr...
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