The latch state is thought to reflect a slowing of the cross-bridge cycle, so that the myosin heads remain in contact with the actin filament for a longer time, thereby maintaining tension at low energy cost. Note that the intracellular [Ca++] falls to a low level during the tonic phase of contraction, though it is still above the resting/ basal [Ca++]. The mechanism contributing to the ability of smooth muscle to maintain force at a low intracellular [Ca++] during tonic contraction is thought to involve dephosphorylation of the myosin regulatory light chain while the myosin cross-bridge is attached to the actin filament, resulting in slowing of the rate of dissociation of the myosin from the actin, allowing the myosin to spend more time in an attached, force-generating conformation. Relaxation of smooth muscle following tonic contraction occurs when intracellular [Ca++] decreases to a level that prevents a net phosphorylation of the regulatory light chain by MLCK. It has also been proposed that caldesmon may participate in the transition to the latch state.
As already noted, ATP consumption is reduced during the latch state. Under this condition, smooth muscle uses 300fold less ATP than would be required by skeletal muscle to generate the same force. Smooth muscle, like skeletal muscle, requires ATP for ion transport to maintain the resting membrane potential, sequester Ca++ in the SR, and extrude Ca++ from the cell. All these metabolic needs are readily met by oxidative phosphorylation. Fatigue of smooth muscle does not occur unless the cell is deprived of oxygen. However, aerobic glycolysis with lactic acid production normally supports membrane ion pumps even when oxygen is plentiful.
Regulation of Myoplasmic Calcium Concentration
The mechanisms that couple activation to contraction in smooth muscle involve two Ca++ sources: one involving the sarcolemma and the other involving the SR. The sarcolemma regulates Ca++ influx and efflux from the extracellular Ca++ pool. The SR membranes determine Ca++ movement between the myoplasm and the SR pool. Skeletal muscle contraction does not require extracellular Ca++ (see ). In contrast, extracellular Ca++ is important for smooth muscle contraction. Thus regulation of myoplasmic [Ca++] involves not only the SR but also the sarcolemma (
Fig. 14.10). A number of factors can alter the myoplasmic
Na+-K+ pump 2K+ 3 Na+ Ca++ MLCK off CaCM CM ATP Receptor-activated CaCM*MLCK ATP G G Sarcoplasmic reticulum Time IP3 PIP2 3Na Cell Ca++ Neurotransmitter or hormone Neurotransmitter or hormone Ca++ channel Refilling ATP ?