Harpers

566 / CHAPTER 49Table 49–2. Some other important proteinsof muscle.Protein Location Comment or FunctionTitin Reaches from the Z Largest protein in body.line to the M line Role in relaxation ofmuscle.Nebulin From Z line along May regulate assemblylength of actin and length of actinfilamentsfilaments.α-Actinin Anchors actin to Z Stabilizes actinlinesfilaments.Desmin Lies alongside actin Attaches to plasmafilamentsmembrane (plasmalemma).Dystrophin Attached to plasma- Deficient in Duchennelemmamuscular dystrophy.Mutations of its genecan also cause dilatedcardiomyopathy.Calcineurin Cytosol A calmodulin-regulatedprotein phosphatase.May play importantroles in cardiac hypertrophyand in regulatingamounts of slow andfast twitch muscles.Myosin- Arranged trans- Binds myosin and titin.binding versely in sarcomere Plays a role in mainproteinC A-bandstaining the structuralintegrity of the sarcomere.Deletion of part of the structural gene for dystrophin,located on the X chromosomeDiminished synthesis of the mRNA for dystrophinLow levels or absence of dystrophinMuscle contraction/relaxation affected;precise mechanisms not elucidatedProgressive, usually fatal muscular weaknessFigure 49–11. Summary of the causation ofDuchenne muscular dystrophy (MIM 310200).Duchenne muscular dystrophy. Mutations in the genesencoding some of the components of the sarcoglycancomplex shown in Figure 49–12 are responsible forlimb-girdle and certain other congenital forms of musculardystrophy.CARDIAC MUSCLE RESEMBLES SKELETALMUSCLE IN MANY RESPECTSThe general picture of muscle contraction in the heartresembles that of skeletal muscle. Cardiac muscle, likeskeletal muscle, is striated and uses the actin-myosintropomyosin-troponinsystem described above. Unlikeskeletal muscle, cardiac muscle exhibits intrinsic rhythmicity,and individual myocytes communicate witheach other because of its syncytial nature. The T tubularsystem is more developed in cardiac muscle,whereas the sarcoplasmic reticulum is less extensiveand consequently the intracellular supply of Ca 2+ forcontraction is less. Cardiac muscle thus relies on extracellularCa 2+ for contraction; if isolated cardiac muscleis deprived of Ca 2+ , it ceases to beat within approximately1 minute, whereas skeletal muscle can continueto contract without an extracellular source of Ca 2+ .Cyclic AMP plays a more prominent role in cardiacthan in skeletal muscle. It modulates intracellular levelsof Ca 2+ through the activation of protein kinases; theseenzymes phosphorylate various transport proteins inthe sarcolemma and sarcoplasmic reticulum and also inthe troponin-tropomyosin regulatory complex, affectingintracellular levels of Ca 2+ or responses to it. Thereis a rough correlation between the phosphorylation ofTpI and the increased contraction of cardiac muscle inducedby catecholamines. This may account for the inotropiceffects (increased contractility) of β-adrenergiccompounds on the heart. Some differences amongskeletal, cardiac, and smooth muscle are summarized inTable 49–3.Ca 2+ Enters Myocytes via Ca 2+ Channels& Leaves via the Na + -Ca 2+ Exchanger& the Ca 2+ ATPaseAs stated above, extracellular Ca 2+ plays an importantrole in contraction of cardiac muscle but not in skeletalmuscle. This means that Ca 2+ both enters and leavesmyocytes in a regulated manner. We shall briefly considerthree transmembrane proteins that play roles inthis process.A. Ca 2+ CHANNELSCa 2+ enters myocytes via these channels, which allowentry only of Ca 2+ ions. The major portal of entry is the