Chapter 31 - Vascular Smooth Muscle Contraction

Abstract

Smooth muscle contraction occurs via a sliding filament mechanism similar to that in striated muscles. The contractile apparatus of smooth muscle consists of the contractile proteins—actin/tropomyosin and myosin that are organized into thin and thick filaments, respectively—and associated regulatory proteins—myosin light chain kinase (MLCK), calmodulin (CaM), myosin light chain phosphatase (MLCP), caldesmon, and calponin. Although smooth muscles contain about one-third the amount of myosin and more actin and tropomyosin than striated muscles, they are still capable of generating similar stresses. The principal mechanism of regulation of smooth muscle contraction involves a thick filament-linked process, myosin phosphorylation–dephosphorylation. In addition, evidence supports thin filament linked regulation that can modulate or fine-tune the contractile state of smooth muscles and involves the actin-binding proteins, calponin, and caldesmon. Phosphorylation of smooth muscle myosin plays a central role in the regulation of smooth muscle contraction. Myosin phosphorylation has been characterized thoroughly both in vitro and in vivo and is catalyzed by Ca2+/CaM-dependent MLCK. Specific phosphorylation occurs at serine 19 in each of the two 20-kDa light chains. Under some circumstances, phosphorylation can also occur at the neighboring threonine 18. Phosphorylation is Ca2+ and CaM dependent and results in a substantial increase in actin-activated myosin MgATPase activity. Contractile abnormalities of smooth muscle are major causes of disease such as asthma, high blood pressure, coronary artery disease, and cerebral vasospasm following subarachnoid hemorrhage. An excess of excitatory agonists, such as histamine in allergy, causes bronchoconstriction and asthmatic symptoms. Enhanced responsiveness of vascular smooth muscles to normal stimuli results in vasoconstriction and increased blood pressure.