an ATP molecule is also needed to energize the myosin cross-bridge for the development of force.
TheentericnervoussystemcontrolsmanyaspectsofGIfunction,includingmotility.Somechildrenarebornwithoutentericnervesinthedistalportionofthecolon.Theabsenceofnervesiscausedbymutantgenesthatdisruptthesignalsnecessaryfortheembryonicnervestomigratetothecolon.Inthesechildren,normalmotilityofthecolondoesnotoccurandsevereconstipationresults.ThisconditioniscalledHirschsprung’s disease. Itcanbecorrectedbysurgicallyremovingtheportionofthecolonthatdoesnotcontainentericnerves.
Contraction of smooth muscle is thus said to be thick-filament regulated, which contrasts with the thin-filament regulation of contraction of striated muscle, where binding of Ca++ to troponin exposes myosin binding sites on the actin thin filament. The thick-filament regulation is attributable to expression of a distinct myosin isoform in smooth muscle.
The myosin cross-bridge cycle in smooth muscle is similar to that in striated muscle in that after attachment to the actin filament, the cross-bridge undergoes a ratchet action in which the thin filament is pulled toward the center of the thick filament and force is generated. ADP and Pi are released from the myosin head at this time, thereby allowing ATP to bind. ATP decreases the affinity of myosin for actin, which allows release of myosin from actin. Energy from the newly bound ATP is then used to produce a conformational change in the myosin head (i.e., recocking the head) so that the cross-bridge is ready for another contraction cycle. The cross-bridge cycle continues as long as the myosin cross-bridge remains phosphorylated. Note that although the four basic steps of the cross-bridge cycle appear to be the same for striated and smooth muscle, the kinetics of cross-bridge cycling is much slower for smooth muscle.
Cross-bridge cycling continues with the hydrolysis of 1 ATP molecule per cycle until myoplasmic [Ca++] falls. With the decrease in [Ca++], MLCK becomes inactive, and the cross-bridges are dephosphorylated by MP (see
Fig. 14.7
Fig. 14.4 , the thin filaments in smooth muscle are attached to dense bodies, and the myosin thick filaments appear to reside between two dense bodies and overlap a portion of the thin filaments, much like the overlap of thick and thin filaments in the sarcomere of striated muscle. A bipolar arrangement of myosin molecules within the thick filament is thought to allow the myosin cross-bridges to pull the actin filaments toward the center of the thick filament, thus contracting the smooth muscle and hence developing force.
From a structural standpoint, smooth muscle myosin is similar to striated muscle myosin in that they both contain a pair of heavy chains and two pairs of light chains. Despite this similarity, they represent different gene products and thus have different amino acid sequences. As noted, smooth muscle myosin, unlike skeletal muscle myosin, is unable to interact with the actin thin filament unless the regulatory light chain of myosin is phosphorylated. Moreover, the thin filament in smooth muscle lacks troponin, which plays a •Fig. 14.7 RegulationofsmoothmusclemyosininteractionswithactinbyCa++-stimulatedphosphorylation.Intherelaxedstate,cross-bridgesarepresentasahigh-energymyosin-ADP-PicomplexinthepresenceofATP.Attachmenttoactindependsonphosphorylationofthecross-bridgebyaCa++-calmodulin–dependentmyosinlight-chainkinase(MLCK).Phosphorylatedcross-bridgescycleuntiltheyaredephosphorylatedbymyosinphosphatase.Notethatcross-bridgephosphorylationataspecificsiteonamyosinregulatorylightchainrequiresATPinadditiontothatusedineachcyclicinteractionwithactin.
critical role in the thin-filament regulation of contraction in striated muscle (see