Vascular smooth muscle (VSM) contraction is, like that of cardiac muscle, controlled by the intracellular Ca²⁺ concentration [Ca²⁺]_i. Unlike cardiac muscle cells, however, VSM cells lack troponin and utilize a myosin-based system to regulate contraction.

Regulation of Contraction by Ca²⁺ and Myosin Phosphorylation (See Shaded Area in Left Cell of Figure 15)

Vasoconstricting stimuli initiate VSM cell contraction by increasing [Ca²⁺]_i from its basal level of ∼100 nmol/L. Force development is proportional to the increase in [Ca²⁺]_i, with maximal contraction occurring at ∼1 µmol/L [Ca²⁺]_i. The rise in [Ca²⁺]_i promotes its binding to the cytoplasmic regulatory protein calmodulin (CaM). Once a calmodulin molecule has bound four Ca²⁺ ions, it can activate the enzyme myosin light-chain kinase (MLCK). MLCK in turn phosphorylates two 20-kDa subunits (‘light chains’) contained within the ‘head’ of each myosin molecule. Phosphorylated myosin then forms crossbridges with actin, using ATP hydrolysis as an energy source to produce contraction. Actin–myosin interactions during crossbridge cycling are similar to those in cardiac myocytes (see Chapter 12).

The degree of myosin light-chain phosphorylation, which determines crossbridge turnover, is a balance between the activity of MLCK and a myosin light-chain phosphatase which dephosphorylates the light chains. Once [Ca²⁺]_i falls, MLCK activity diminishes and relaxation occurs as light-chain phosphorylation is returned to basal levels by the phosphatase.

VSM cells in vivo maintain a tonic level of partial contraction that varies with fluctuations in the vasoconstricting and vasodilating influences to which they are exposed. VSM cells avoid fatigue during prolonged contractions because their rate of ATP consumption is 300-fold lower than that of skeletal muscle fibres. This is possible because the crossbridge cycle is much slower than in striated muscles. The maximum crossbridge cycling rate of smooth muscle during shortening is only about one-tenth of that in striated muscles, as a result of differences in the types of myosin present. In addition, once they have shortened, vascular cells can maintain contraction with an even lower expenditure of ATP because the myosin crossbridges remain attached to actin for a longer time, thus ‘locking in’ shortening.

Vasoconstricting Mechanisms

The binding to receptors of noradrenaline and other important vasoconstrictors such as endothelin, thromboxane A₂, angiotensin II and vasopressin stimulates VSM contraction via common G-protein–mediated pathways (see left cell).

Effects of IP₃ and Diacylglycerol

Binding of vasoconstrictors to receptors activates the G-protein Gq, which stimulates the enzyme phospholipase C. Phospholipase C splits the membrane phospholipid phosphatidylinositol 1,4-bisphosphate (PIP₂

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