The T tubules in cardiac muscle are positioned at the Z lines, whereas in mammalian skeletal muscle, they are positioned at the ends of the I bands. The connections between the T tubules and the SR are fewer and less developed in cardiac muscle compared to skeletal muscle.
Familial cardiomyopathic hypertrophy (FCH) occurs in approximately 0.2% of the general population but is a leading cause of sudden death in otherwise healthy adults. Genetic defects in various proteins in cardiac sarcomeres, including myosin, troponin, tropomyosin, and myosin-binding protein C, have been linked to FCH. Myosin-binding protein C is a structural protein located in the middle of the A band of the sarcomere. FCH is an autosomal dominant disease, and transgenic studies suggest that even a small amount of the mutated protein can result in the development of the cardiomyopathic phenotype. Furthermore, a single amino acid mutation in the myosin molecule is sufficient to produce cardiomyopathic hypertrophy. The pathogenesis of FCH is variable, even within a family with a single gene defect, suggesting the presence of modifying loci.
Control of Cardiac Muscle Activity
Cardiac muscle is an involuntary muscle with an intrinsic pacemaker located in the sinoatrial node of the right atrium. The pacemaker cell can undergo spontaneous depolarization and generate action potentials. While multiple cells in the heart can depolarize spontaneously, the fastest depolarizations occur in the sinoatrial node. Once a cell depolarizes and fires an action potential, it is propagated throughout the heart via specialized conduction pathways and cell-to-cell contact. Therefore, only one cell's depolarization is needed to initiate a wave of contraction, or a heartbeat. The mechanisms underlying this spontaneous depolarization are discussed in depth in Figure 16.17. After an action potential is initiated in the sinoatrial node, it is propagated between atrial cells through gap junctions and specialized conduction fibers in the atria. The action potential can travel through the entire atria in approximately 70 msec. To reach the ventricles, the action potential must pass through the atrioventricular node. Afterward, it passes through the ventricle via specialized conduction pathways (the bundle of His and the Purkinje system) and gap junctions in the intercalated disks of adjacent cardiac myocytes. The action potential can pass through the entire heart within 220 msec after initiation in the sinoatrial node. Since the contraction of a cardiac muscle cell typically lasts 300 msec, this rapid conduction promotes nearly synchronous contraction of heart muscle cells. This is different from skeletal muscle, where cells are grouped into motor units that are recruited independently as the force of contraction increases.
The sarcolemma of cardiac muscle also contains invaginations (T tubules) comparable to those seen in skeletal muscle. In cardiac muscle, however, T tubules are positioned at the Z lines, whereas in mammalian skeletal muscle, T tubules are positioned at the ends of the I bands. In cardiac muscle, the connections between the T tubules and the SR are fewer than, and not as well developed as, those in skeletal muscle.
Familial cardiomyopathic hypertrophy (FCH) occursinapproximately0.2%ofthegeneralpopulationbutisaleadingcauseofsuddendeathinotherwisehealthyadults.Ithasbeenlinkedtogeneticdefectsinavarietyofproteinsincardiacsarcomeres,includingmyosin,troponin,tropomyosin,andmyosin-bindingproteinC,astructuralproteinlocatedinthemiddleoftheAbandofthesarcomere.FCHisanautosomaldominantdisease,andtransgenicstudiesindicatethatexpressionofonlyasmallamountofthemutatedproteincanresultindevelopmentofthecardiomyopathicphenotype.Moreover,mutationofasingleaminoacidinthemyosinmoleculeissufficienttoproducecardiomyopathichypertrophy.ThepathogenesisofFCH,however,isvariable,evenwithinafamilywithasinglegenedefect,intermsofbothonsetandseverity;thisvariabilitysuggeststhepresenceofmodifyingloci.
Control of Cardiac Muscle Activity
Cardiac muscle is an involuntary muscle with an intrinsic pacemaker. The pacemaker represents a specialized cell (located in the sinoatrial node of the right atrium) that is able to undergo spontaneous depolarization and generate action potentials. Of importance is that although several cells in the heart are able to depolarize spontaneously, the fastest spontaneous depolarizations occur in cells in the sinoatrial node. Moreover, once a given cell spontaneously depolarizes and fires an action potential, this action potential is then propagated throughout the heart (by specialized conduction pathways and cell-to-cell contact). Thus depolarization from only one cell is needed to initiate a wave of contraction in the heart (i.e., a heartbeat). The mechanisms underlying this spontaneous depolarization are discussed in depth in
Fig. 16.17 , once an action potential is initiated in the sinoatrial node, it is propagated between atrial cells via gap junctions, as well as through specialized conduction fibers in the atria. The action potential can pass throughout the atria within approximately 70 msec. For the action potential to reach the ventricles, it must pass through the atrioventricular node, after which the action potential passes throughout the ventricle via specialized conduction pathways (the bundle of His and the Purkinje system) and gap junctions in the intercalated disks of adjacent cardiac myocytes. The action potential can pass through the entire heart within 220 msec after initiation in the sinoatrial node. Because contraction of a cardiac muscle cell typically lasts 300 msec, this rapid conduction promotes nearly synchronous contraction of heart muscle cells. This is a very different scenario from that of skeletal muscle, in which cells are grouped into motor units that are recruited independently as the force of contraction is increased.