How is the contraction of smooth muscle regulated? The smooth muscle that controls many internal organs can be activated by the autonomic nervous system and also responds to stretch of the muscle, local hormones, and other local factors such as pH, oxygen, carbon dioxide, and nitric oxide by intracellular signaling. For example, smooth muscle in the walls of arteries contracts when stimulated by the release of epinephrine to reduce blood flow to a body region (Chapter 39), and smooth muscle within the mammalian uterus contracts when oxytocin is released to stimulate contractions (Chapter 42). As in skeletal muscle, these initiators trigger the release of Ca²⁺ from the SR. However, in smooth muscle, Ca²⁺ also enters through voltage-gated and stretch-receptor calcium channels in the cell’s plasma membrane.

Smooth muscle lacks the troponin–tropomyosin mechanism for regulating contraction. Instead, activation of smooth muscle cells results when the protein calmodulin binds with Ca²⁺ released from the SR or entering through the cell’s membrane. The calmodulin–Ca²⁺ complex activates a myosin kinase that phosphorylates the smooth muscle myosin heads, causing them to bind actin and begin the cross-bridge cycle. A second enzyme dephosphorylates the myosin heads, disrupting their ability to bind to actin, and the muscle relaxes.

Smooth muscle contracts slowly compared with skeletal muscle, using less ATP per unit time. The SR of smooth muscle cells is less extensive and has many fewer calcium pumps than the SR of skeletal muscle cells. As a result, calcium is returned more gradually from the myofibrils back to the SR, or pumped back out through the cell’s membrane, slowing the relaxation of smooth muscle. Using the slow contractions of smooth muscle, clams hold their shells closed for long periods, arteries contract and restrict blood flow to particular body regions, and the gut moves digestive contents through the gastrointestinal tract.