The force of contraction in cardiac muscle increases when it is stretched within a specific range of sarcomere lengths (approximately 1.6-2.3 um). This increase occurs rapidly and can happen within a single heartbeat. The mechanism behind this stretch-induced increase in force is still debated, but it seems to involve changes in the overlap of thick and thin filaments and an increase in the calcium sensitivity of contraction. About 60% of the stretch-induced increase in force is attributed to the increase in calcium sensitivity, while the remaining 40% is attributed to changes in filament overlap. However, the changes in filament overlap are less likely to contribute to the force increase as sarcomere length increases beyond 2.0 um. The increase in calcium sensitivity of contraction is thought to involve the protein titin and regulatory proteins such as troponin C. Similar to skeletal muscle, cardiac muscle also uses ATP to generate force, and this ATP pool needs to be continuously replenished through aerobic metabolism. During ischemic conditions, the creatine phosphate pool, which converts ADP to ATP, may decrease. In rat ventricular trabecular muscle, the creatine phosphate pool is relatively small.
This stretch-induced increase in force of contraction of cardiac muscle occurs over a narrow range of sarcomere lengths (ca. 1.6-2.3 um), resulting in a steep length-dependent activation of contraction. This ascending limb of the length-tension relationship in cardiac muscle is much steeper than that seen in skeletal muscle. It is important to note that this stretch-induced increase in force can occur within a singe heart beat.
The mechanism(s) underlying this stretch-induced increase in force of contraction of cardiac muscle is controversial, but appears to involve changes in the overlap of the thick and thin filaments as well as stretch-induced increase in the Ca++ sensitivity of contraction (
Fig. 13.6B of the stretch-induced increase in force of contraction has been attributed to an increase in Ca++ sensitivity, whereas the remaining 40% of the stretch-induced increase in force of contraction has been attributed to changes in the overlap of the thick and thin filaments. The changes in myofilament overlap, however, are less likely to contribute to the continued increase in force of cardiac contraction as sarcomere length increases from 2.0um to 2.3 um, as this region is thought to represent a region of optimal overlap of myofilaments (and represents a plateau in the length tension relationship in skeletal muscle).
The mechanism(s) contributing to the stretch-induced increase in Ca++ sensitivity of cardiac contraction are not clear, but appears to involve the intracellular elastic protein titin, as well as regulatory proteins (e.g., troponinC).
As in skeletal muscle, myosin uses the energy in ATP to generate force, so the ATP pool, which is small, must be continually replenished. Typically, this replenishment of ATP pools is accomplished by aerobic metabolism, including the oxidation of fats and carbohydrates. During times of ischemia, the creatine phosphate pool, which converts ADP to ATP, may decrease. As in skeletal muscle, the
In rat ventricular trabecular muscle, approximately 60% creatine phosphate pool is small.
276 SECTION3Berne & Levy Physiology ContractionSarcomereCa2˜Ca2˜Ca2˜Sarcomere RelaxationSarcoplasm MyocyteSarcoplasmic reticulum RyRSERCASERCAPLNDWORF A B C 125 100 75 50 25 0 250 200 150 100 50 0 WT Tg KO % Vmax 8.0 7.5 7.0 6.5 6.0 5.5 pCa * * WT Tg KO KCa[Ca2˜]free (nM) •Fig. 13.5 Asmall(34–aminoacid)peptideencodedbyalongnoncodingRNAappearstoimprovesarcoplasmicreticulumfunctionandmyocyteperformancebycounteringtheinhibitoryeffectofphospholamban(PLN)(asdepictedintheworkingmodelshowninpanelA).TheabilityofDWORFtoincreasecardiacSRCauptakeisshowninpanelsBandC,whereoverexpressionofDWORFincardiomyocytes(labeledTg)increasedtheCasensitivityofSRCatransport,whereasknockoutofDWORF(labeledKO)hadthereverseeffect.DWORF,dwarfopenreadingframe;KO,knockout;SERCA,sarcoplasmicendoplasmicreticulumcalcium-ATPase;Tg,transgenic;WT,wild-type.(FromNelsonBR,MakarewichCA,AndersonDM,etal.ApeptideencodedbyatranscriptannotatedaslongnoncodingRNAenhancesSERCAactivityinmuscle.Science. 2016;351:271-275.)