A characteristic feature of smooth muscle cells is the presence of large numbers of invaginations of the cell membrane that resemble caveolae (see Fig. 11.19). Beneath the plasma membrane, and often in proximity to the sparse profiles of the sER, are cytoplasmic vesicles. It is thought that the invaginations of the cell membrane and the underlying vesicles along with the sER function in a manner analogous to the T system of striated muscle to deliver Ca2 to the cytoplasm. Intracellular Ca2 concentrations are very important in regulating smooth muscle contraction.
An elevation of intracellular Ca2 levels in smooth muscle is achieved either by depolarization of the cell membrane with subsequent activation of voltage-sensor proteins or by direct activation of gated Ca2-release channels in the sER by a second-messenger molecule, most commonly IP3. The IP3 receptor is located in the sER membrane and has properties similar to those of gated Ca2-release channels. The amount of Ca2 entering the cell after activation of the voltage-sensor protein is usually insufficient to initiate smooth muscle contraction and needs to be supplemented by release of Ca2 from the sER. The Ca2 then binds to calmodulin, which activates phosphorylation of the myosin light chain kinase to initiate contraction. After the contraction cycle commences, Ca2 is removed from the sarcoplasm by ATP-dependent calcium pumps and resequestered in the sER or delivered to the extracellular environment.
Contraction of smooth muscle is regulated by the Ca2–calmodulin–myosin light chain kinase system.
A modified version of the sliding filament model described on page 323 can explain contraction in both striated and smooth muscle (see Fig. 11.22). As in striated muscle, contraction is initiated by an increase in the Ca2 concentration in the cytosol, but the contraction does not act through a troponin–tropomyosin complex on the thin filament. Rather, in smooth muscle, an increase in Ca2 concentration stimulates a myosin light chain kinase (MLCK) to phosphorylate one of the two regulatory light chains of the myosin molecule. The Ca2 binds to calmodulin to form the Ca2–calmodulin complex, which in turn binds to MLCK to activate the phosphorylation reaction of the regulatory light chain of myosin (Fig. 11.23). When the light chain is phosphorylated, the actin-binding site of the myosin head is activated and attaches to actin. In the presence of ATP, the myosin head bends, producing contraction. When it is dephosphorylated, the myosin head dissociates from actin. This phosphorylation occurs slowly, with maximum contraction often taking up to a second to achieve.
Smooth muscle cell myosin hydrolyzes ATP at about 10% of the rate of skeletal muscle, producing a slow cross-bridging cycle that results in slow contraction of these cells. Thus, smooth muscle cells, and nonmuscle cells that contract by this same mechanism, are capable of sustained contractions over long periods of time while using only 10% of the ATP that would be used by a striated muscle cell performing the same work.
The force of smooth muscle contraction may be maintained for long periods in a “latch state.”
In addition to normal phosphorylation of the regulatory light chains of myosin, smooth muscle cells possess a secondary mechanism that allows them to maintain long-term contraction with minimal expenditure of ATP. This mechanism is detected in vascular smooth muscles, for example, and is used to maintain the force of contraction (tone of blood vessels) for an extended time. This so-called latch state of smooth muscle contraction occurs after the initial Ca2-dependent myosin phosphorylation. The myosin head attached to the actin molecule becomes dephosphorylated, causing its ATPase activity to decrease. As a result of the decrease in ATP activity, the myosin head is unable to detach from the actin flament, which maintains the contracted state. The latch state is comparable in many ways to rigor mortis in striated muscle.