Introduction
Smooth muscle cells line blood vessels, airways, and many hollow organs. Unlike skeletal muscle—which relies solely on a precise electrical impulse from a motor neuron—smooth muscle responds to chemical, electrical, and mechanical cues. Central to every contraction is the rise and fall of cytoplasmic calcium.
Sources of Calcium
Most calcium that triggers smooth muscle contraction enters from outside the cell. Chemical messengers such as epinephrine or acetylcholine bind G protein–coupled receptors on the membrane, activating phospholipase C. This enzyme produces inositol trisphosphate (IP₃), which diffuses to the sarcoplasmic reticulum (SR) and opens IP₃-gated channels. Stored calcium then floods into the cytoplasm.
Concurrently, small changes in membrane voltage open L-type voltage-gated calcium channels. Calcium entering through these channels can further provoke SR release via ryanodine receptors in a process called calcium-induced calcium release. Together, these pathways ensure that both chemical and electrical signals can elevate intracellular calcium.
Calcium’s Role in Contraction
Once cytoplasmic calcium rises, it binds calmodulin, forming a complex that activates myosin light chain kinase (MLCK). MLCK phosphorylates the regulatory light chain on myosin II, increasing its ATPase activity so myosin can bind actin and generate force. As myosin walks along actin filaments, the cell shortens and tension develops.
Smooth muscle then conserves energy by entering a “latch state.” Myosin light chains may become dephosphorylated by myosin phosphatase, yet myosin remains attached to actin, holding force with very low ATP consumption.
Relaxation Mechanism
Relaxation begins as calcium is removed from the cytoplasm. Pumps in the cell membrane and SR actively transport calcium back out or into stores. Reduced cytoplasmic calcium causes calmodulin to release MLCK, and myosin phosphatase removes phosphates from myosin. Without phosphorylation, myosin detaches from actin and the cell relaxes.
Comparison with Skeletal Muscle
Skeletal muscle relies on a single mechanism: a motor neuron action potential triggers the dihydropyridine receptor on the T-tubule, mechanically opening ryanodine receptors on the SR. Released calcium binds troponin, shifting tropomyosin off actin’s binding sites and allowing rapid, all-or-none twitches. In contrast, smooth muscle uses multiple initiation routes—chemical agonists, voltage changes, even stretch—and regulates contraction via calmodulin/MLCK rather than troponin.
Physiological Significance
Smooth muscle’s graded response and energy-efficient latch state make it ideal for maintaining blood vessel tone, regulating airway diameter, and driving peristalsis. Its ability to integrate hormonal, autonomic, and local signals allows tissues to adjust blood flow, bronchial resistance, and organ motility to meet changing physiological demands.
