Cardiac Muscle Contraction

Aka, automaticity Pacemaker cells within the sinoatrial (SA) node of the heart spontaneously depolarize. Neural input is not required, though both neural and hormonal factors can affect the rate of depolarization. Gap junctions between cardiac muscle cells allow depolarization waves to travel rapidly from cell to cell, so that the heart contracts as atrial and ventricular units. Clinical correlations: Arrhythmias (AV node block, Supraventricular, Ventricular) Recall that, in contrast, each skeletal muscle fiber is innervated by a nerve ending. The mechanism linking action potentials to myofibril contractions. Influx of calcium ions from both the extracellular fluid and sarcoplasmic reticulum are necessary for myofibril contraction. Recall that skeletal muscle EC coupling requires only sarcoplasmic reticulum calcium release. As in skeletal muscle, cardiac muscle contraction requires binding of the thin and thick filaments and cross-bridge cycling to shorten the sarcomere and create muscle tension. Each myofibril comprises proteins, notably the thick and thin myofilaments, which overlap to form contractile units called sarcomeres. Z-discs anchor the thin filaments. Thick filaments extend from the perpendicular M line in the spaces between thin filaments. The I band, aka, light band, of the myofibril comprises the area where there is no overlap between thick and thin filaments (think I for lIght). The area where thick and thin filaments do overlap creates the A band, aka, dark band (think A for dArk). The Sarcomere spans from z-disc to z-disc; the sarcomere is the functional contractile unit of the myofibrils. Thick filaments: feature the protein myosin; the head has the actin binding site, the tails intertwine. During contraction, the myosin heads bind with actin to form cross bridges. Thin filaments: actin is the primary protein; it comprises multiple polypeptide subunits (called globular actin) arranged in a double helix. Actin has myosin binding sites. Tropomyosin strands wrap around the actin molecules and, in a relaxed state, cover their myosin binding sites. Troponin is a three-polypeptide complex; one of the polypeptides serves as a calcium binding site. To summarize the relationship between calcium and cross-bridge cycling: 1) Troponin binds intracellular calcium, causing 2) Tropomyosin movement and exposure of the myosin-binding sites, allowing 3) Myosin-actin binding and cross bridge cycling to shorten the sarcomeres. Contraction via the sliding filament mechanism occurs as in skeletal muscle, which is discussed in detail, elsewhere. 1) An action potential is generated, typically by pacemaker cells in the sinoatrial node, and is then transferred from cell to cell via gap junctions. 2) As the action potential travels along the sarcolemma, it triggers the opening of the voltage-gated L-type calcium channels; this allows calcium to move down its electrochemical gradient into the cell. 3) Calcium influx opens the ryanodine receptors on the sarcoplasmic reticulum, and large quantities of calcium ions move into the intracellular fluid. 4) Calcium-induced calcium release from the SR creates a calcium "spark," which amplifies the calcium signal. 5) Calcium binds troponin and, ultimately, allows cross-bridge cycling and sarcomere shortening to contract the myocardial cells. 6) Muscle cells cannot be in a state of constant contraction; calcium influx ends when the channels close, but we also need to remove the calcium already present in the intracellular fluid. This is achieved by the continuous action of the SERCA and sodium-calcium exchangers, which move calcium into the sarcoplasmic reticulum and extracellular space, respectively. More specifically, the sodium-calcium exchanger exchanges three sodium molecules for a single calcium molecule; the sodium is then pumped out of the cell via sodium-potassium ATPase (not shown for simplicity). 7) As a result of reduced intracellular stores and troponin's release of calcium, cross-bridge cycling stops, and the sarcomere relaxes. Contractility (aka, inotropism) refers to the intrinsic ability of cardiac muscle cells to produce force at a given cell length. Contractility can be increased or decreased by various factors, including the availability of calcium. For example, cardiac glycosides, which are derived from the digitalis plant, raise intracellular calcium concentrations and, therefore, increases contractility. Thus, cardiac glycosides are prescribed for heart failure. On the other hand, calcium channel blockers block the L-type calcium channels and prohibit calcium influx, and, therefore, reduce contractility. They are prescribed as treatment for hypertension, angina, and some arrhythmias. Review: Cardiac Conduction Pathway