Regulation of Contraction in Cardiac Muscle Is Also Actin-Based

Cardiac muscle, like skeletal muscle, is striated. It also is regulated by a similar actin-myosin-tropomyosin-troponin system. Unlike skeletal muscle, cardiac muscle exhibits intrinsic rhythmicity, and individual myocytes communicate with each other because of its syncytial nature. The T-tubular system is more developed in cardiac muscle, whereas the SR is less extensive and consequently the intracellular supply of Ca2+ for contraction is lower. Cardiac muscle thus relies on extracellular Ca2+ for contraction; if isolated cardiac muscle is deprived of Ca2+, it ceases to beat within approximately 1 minute, whereas skeletal muscle can continue to contract without an extracellular source of Ca2+ for a longer period. Cyclic AMP (cAMP) plays a more prominent role in cardiac muscle than it does in skeletal muscle. cAMP modulates intracellular levels of Ca2+ through the activation of the protein kinases that phosphorylate various transport proteins in the sarcolemma and SR. The protein kinases also target the troponin-tropomyosin regulatory complex, affecting its responsiveness to intracellular Ca2+. There is a rough correlation between the phosphorylation of TpI and the increased contraction of cardiac muscle induced by catecholamines. This may account for the inotropic effects (increased contractility) of β-adrenergic compounds on the heart. Some differences among skeletal, cardiac, and smooth muscle are summarized in Table 1.

Table1. Some Differences Among Skeletal, Cardiac, & Smooth Muscle

Ca2+ Enters Cardiomyocytes via Ca2+ Channels & Leaves via the Na+-Ca2+ Exchanger & the Ca2+ ATPase

Extracellular Ca2+ enters cardiomyocytes via highly selective channels. The major portal of entry is the L-type (long-duration current, large conductance) or slow Ca2+ channel, which is voltage-gated, opening during depolarization and closing when the action potential declines. These channels are equivalent to the dihydropyridine receptors of skeletal muscle. Slow Ca2+ channels are regulated by cAMP-dependent protein kinases (stimulatory) and cGMP-dependent protein kinases (inhibitory), and can be inhibited by so-called calcium channel blockers (eg, verapamil). Fast (or T, transient) Ca2+ channels are also present in the plasmalemma, though in much lower numbers; they probably contribute to the early phase of increase of myoplasmic [Ca2+].

When the [Ca2+] in the myoplasm increases, it triggers the opening of the Ca2+ release channel of the SR. This Ca2+ induced Ca2+ release from the SR stores accounts for approximately 90% of the Ca2+ that enters a stimulated cardiomyocyte. However, the 10% that enters from the cytoplasm is vitally important, as it serves as a trigger for mobilization of Ca2+ from the SR.

The Na+-Ca2+ exchanger serves as the principal route of egress of Ca2+ from cardiomyocytes. Na+ and Ca2+ are exchanged at a ratio of 3:1, with movement of Na+ into the cell from the plasma providing the energy needed to move Ca2+ into the plasma against a concentration gradient. The Na+ Ca2+ exchange contributes to relaxation, but may run in the reverse direction during excitation. Consequently, anything that causes intracellular [Na+] to rise will secondarily cause intracellular [Ca2+] to rise as well, causing more forceful con traction (positive inotropic effect). Digitalis promotes the inflow of Ca2+ via the Ca2+-Na+ exchanger by inhibiting the sarcolemmal Na+-K+-ATPase, reducing the rate of Na+ exit by this route, thereby increasing intracellular [Na+]. The resulting increase in intracellular [Ca2+] enhances the force of cardiac contraction to the benefit of a patient experiencing heart failure (Figure 1).

Fig1. Scheme of how the drug digitalis (used in the treatment of certain cases of heart failure) increases cardiac contraction. Digitalis inhibits the Na+-K+ ATPase (see Chapter 40). This results in less Na+ being pumped out of the cardiac myocyte and leads to an increase of the intracellular [Na+]. In turn, this stimulates the Na+-Ca2+ exchanger so that more Na+ is exchanged outward, and more Ca2+ enters the myocyte. The resulting increased intracellular [Ca2+] increases the force of muscular contraction.

In contrast to skeletal muscle, the sarcolemmal Ca2+ ATPase is a to be a minor contributor to Ca2+ egress as com pared with the Ca2+-Na+exchanger. Ion channels are important in skeletal muscle, as well as in cardiac muscle (see Chapter 40). Mutations in genes encoding ion channels are responsible for a number of relatively rare conditions affecting muscle. These and other diseases due to mutations of ion channels have been termed channelopathies; some are listed in Table 2.

Table2. Some Disorders (Channelopathies) due to Mutations in Genes Encoding Polypeptide Constituents of Ion Channels

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مواضيع ذات صلة

Contraction is Orchestrated by the Second Messenger Ca2+

Muscle Converts Chemical Energy to Mechanical Energy

Cholesterol Side Chain Cleavage Enzyme (p450scc)

Steroidogenic Acute Regulatory Protein (StAR)

Cytochrome P450 Steroid Hydroxylases

Major Protein Components of Muscle Fibers

The Major Components of Cartilage are Type II Collagen & Certain Proteoglycans

Bone is Affected by many Metabolic & Genetic Disorders

The Assembly of Membranes is Complex

Transport Vesicle Formation and Function Involves SNAREs & Other Factors

Misfolded Proteins Undergo Endoplasmic Reticulum Associated Degradation

Proteoglycans & Glycosaminoglycans