Contraction of smooth muscle is regulated by the cytosolic Ca2+ level ([Ca2+]i)b, and the sensitivity to Ca2+ of the contractile elements in response to changes in the environment surrounding the cell. The first sequence of events in regulation includes the binding of endogenous substances, such as

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Calcium Movements, Distribution, and Functions in Smooth Muscle

It has been known for more than 60 years, and suspected for over 100, that alveolar hypoxia causes pulmonary vasoconstriction by means of mechanisms local to the lung. For the last 20 years, it has been clear that the essential sensor, transduction, and effector mechanisms responsible for hypoxic pulmonary vasoconstriction (HPV) reside in the pulmonary arterial smooth muscle cell. The main focus of this review is the cellular and molecular work performed to clarify these intrinsic mechanisms and to determine how they are facilitated and inhibited by the extrinsic influences of other cells. Because the interaction of intrinsic and extrinsic mechanisms is likely to shape expression of HPV in vivo, we relate results obtained in cells to HPV in more intact preparations, such as intact and isolated lungs and isolated pulmonary vessels. Finally, we evaluate evidence regarding the contribution of HPV to the physiological and pathophysiological processes involved in the transition from fetal to neonatal life, pulmonary gas exchange, high-altitude pulmonary edema, and pulmonary hypertension. Although understanding of HPV has advanced significantly, major areas of ignorance and uncertainty await resolution.

Hypoxic pulmonary vasoconstriction.

Cellular mechanisms responsible for hypoxic pulmonary vasoconstriction were investigated in pulmonary arterial cells, isolated perfused lung, and pulmonary artery rings. Three K+ channel antagonist...

Direct role for potassium channel inhibition in hypoxic pulmonary vasoconstriction.

1. The amplitude of the noradrenaline-sensitive Ca stores has been estimated by measuring the amplitude of the transient contraction induced by the agonist in Ca-free solution. or by measuring the amount of 45Ca released under these conditions. 2. The rate of filling of this store after depletion is much faster than the rate of depletion in Ca-free solution, and depends on [Ca]o in the bathing solution. The degree of filling also depends on [Ca]o. 3. At the same [Ca]o the degree of filling is higher in K-depolarized tissues than in control tissues. However at 10 mM-[Ca]o and 5.9 mM-K the amount of Ca taken up by the store is larger than that after loading in 0.2 mM-Ca and 141.4 mM-K, although the tissues remain relaxed during loading at 5.9 mM-K and contracted at 141.4 mM-K. 4. The Ca antagonists D600 and nicardipine selectively block the contraction induced by K depolarization, but do not affect appreciably the noradrenaline-induced contraction. 5. The filling of the store is not significantly reduced by the presence of the Ca antagonists in solutions containing 5.9 mM-K. However these antagonists reduce the degree of filling in K-rich loading solution to a level which is lower than that observed in the control. 6. Mn blocks both the contraction induced by K-rich solution and the tonic component of the noradrenaline-induced contraction and its also inhibits filling of the store. 7. The results suggest that the filling of the store under physiological conditions occurs by a direct pathway between the store and the extracellular medium.

Exchange characteristics of the noradrenaline-sensitive calcium store in vascular smooth muscle cells or rabbit ear artery.

Tetraethylammonium ions and the potassium permeability of excitable cells.

1 The membrane potential of the smooth muscle cells of the rabbit main pulmonary artery amounts to -57 mV, the length constant of the tissue is 148 mm and the time constant of the membrane 182 msec On the basis of the electrical properties of its membrane, this smooth muscle tissue is classified as a single-unit type During outward current pulses, the membrane shows marked rectification and action potentials can never be generated2 Tetraethylammonium (10 mM) and procaine (5 mM) depolarize the membrane and increase the membrane resistance By studying the effect of both substances on the (42)K efflux, it could be concluded that they reduce the K-permeability of the membrane They also suppress the rectification of the membrane and increase the length constant of the membrane In the presence of TEA and procaine, a graded response of the membrane can be induced by outward current pulses, but overshoot potentials never occur3 Noradrenaline, in concentrations between 2 x 10(-8) and 10(-7)M, evokes contraction without depolarizing the membrane When the concentration is increased above 2 x 10(-7)M, noradrenaline depolarizes the membrane and reduces the membrane resistance A study of the effect of noradrenaline on the K, Cl and Na fluxes has revealed that it increases the permeability of the membrane for these three ions4 The tissue concentrations of Na and K are 80 and 38 m-mole/kg wet wt, respectively The amount of Cl in the cellular compartment was measured by an extrapolation procedure and found to be 13 m-mole/kg wet wt The extracellular space measured with [(14)C]sorbitol is 550 ml/kg wet wt and the dry wt/wet wt ratio 19% The calculated equilibrium potentials for K, Na and Cl (E(K), E(Na) and E(Cl)) are -83, +59 and -26 mV, respectively In efflux experiments under steady-state conditions, the following rate constants have been calculated: 0092 min(-1) for Na, 0029 min(-1) for Cl and 00054 min(-1) for K The calculated value for the ratio P(Na)/P(K) was 022 and for P(Cl)/P(K) 0635 K-free solution and 2 x 10(-6)M ouabain depolarize the cells by about 8 mV After exposure of the cells to K-free solution, they hyperpolarize on readmission of K, suggesting that part of the membrane potential could be due to electrogenic transport of ions6 A decrease of external Ca depolarizes the cells and increases the membrane resistance Na-deficiency hyperpolarizes these smooth muscle cells but this procedure does not prevent the depolarization induced by Ca deficiency

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1977.sp011989

The membrane properties of the smooth muscle cells of the rabbit main pulmonary artery.

1. Increasing the external K concentration depolarizes the smooth muscle cells of the main pulmonary artery, and this depolarization reaches a maximal slope of 58 mV for a tenfold change of [K](o). The threshold depolarization for inducing contraction is at 4 mV and the maximal contraction is reached at a [K](o) of 58 mM.2. Noradrenaline concentrations between 2 x 10(-8)M and 10(-7)M induce tension without depolarizing the cells, but at higher concentrations noradrenaline not only elicits a large tension response but also depolarizes the cells in a dose-dependent way.3. The effect of noradrenaline on the pulmonary artery is appreciably modified by substituting sucrose for NaCl: the cells are slightly hyperpolarized and the tension response is very much reduced.4. By studying the tension response to noradrenaline in other experimental conditions which cause a small hyperpolarization of the cells, such as 5 mM-[Ca](o), 2.9 mM-[K](o) or a small depolarization, such as 11.9 mM-[K](o), it was found that a slight modification of the membrane potential can exert an important effect on the noradrenaline response.5. A simultaneous decrease of [Ca](o) and [Na](o) reduces the tension response to all noradrenaline concentrations. It was found that a reduction of [Na](o) exerts a more depressing effect than a reduction of [Ca](o). In interpreting these results we have to take into account changes of the membrane potential, of availability of Ca, and some competition between external Ca and Na.6. A study of the effect of different concentrations of noradrenaline in Krebs solutions and Ca-free solution has shown that concentrations up to 2.5 x 10(-7)M elicit contraction by increasing the Ca influx, while higher concentrations also induce a release of cellular Ca.7. Caffeine depolarizes the cells and reduces the membrane resistance. It modifies the K, Cl and Ca fluxes in the same way as noradrenaline, but it suppresses the mechanical response induced by noradrenaline.

K. Kitamura

Papers

The membrane properties of the smooth muscle cells of the rabbit main pulmonary artery.

Excitation—contraction coupling in the smooth muscle cells of the rabbit main pulmonary artery