The heart relies on extracellular Ca++ for contraction, as demonstrated by the fact that it continues to beat when supplied with a physiological salt solution containing 2 mmol/L Ca++. In contrast, skeletal muscle can contract without extracellular Ca++. Action potentials in cardiac muscle last longer than in skeletal muscle due to a slow inward Ca++ current through voltage-gated L-type calcium channels. This small influx of Ca++ triggers the release of Ca++ from the sarcoplasmic reticulum (SR) and initiates contraction. The L-type calcium channel, composed of five subunits (α1, α2, β, γ, and δ), is present in both skeletal and cardiac muscle but serves different functions in each muscle type. In cardiac muscle, the terminal regions of the SR are adjacent to the T tubules and sarcolemma.
Blood and extracellular fluids typically contain 1 to 2 mmol/L of free Ca++ , and it has been known since the days of the physiologist Sidney Ringer (ca. 1882) that the heart requires extracellular Ca++ to contract. Thus an isolated heart typically continues to beat when perfused with a warm (37°C), oxygenated, physiological salt solution that contains approximately 2 mmol/L Ca++ (e.g., Tyrode’s solution), but it stops beating in the absence of extracellular . This cessation of contractions in Ca++-deficient media is also observed in hearts that are electrically stimulated, which further demonstrates the importance of extracellular Ca++ for contraction of cardiac muscle. This situation is quite different from that of skeletal muscle, which can contract in the total absence of extracellular Ca++ .
Action potentials in cardiac muscle are prolonged, lasting 150 to 300 msec (
Fig. 13.2 inset), which is substantially longer than the action potentials in skeletal muscle (≈5 msec). The long duration of the action potential in cardiac muscle is due to a slow inward Ca++ current through a voltage-gated L-type calcium channel in the sarcolemma. The amount of Ca++ coming into the cardiac muscle cell is relatively small and serves as a trigger for release of Ca++ from the SR. In the absence of extracellular Ca++ , an action potential can still be initiated in cardiac muscle, although it • Fig. 13.2 Excitation-contraction coupling in the heart requires Ca++ influx through L-type calcium channels in the sarcolemma and T tubules. See text for details. Inset shows time course of action potential (AP), intracellular Ca transient (Ca), and contraction. ATP, adenosine triphosphate; NCX, sarcolemmal 3Na+-Ca++ antiporter; PLN, phospholamban; RYR, ryanodine receptor. (Modified from Bers DM. Cardiac excitation-contraction coupling. Nature. 2002;415:198-205. Inset modified from Mountcastle VB: Medical Physiology, 13 ed. St Louis, Mosby, 1974; Brooks CM, Hoffman BF, Suckling EE, Orias O: Excitability of the Heart. New York, Grune & Stratton, 1955.) is considerably shorter in duration and unable to initiate a contraction. Thus influx of Ca++ during the action potential is crucial for triggering release of Ca++ from the SR and thus initiating contraction.
The L-type calcium channel is composed of five subunits (α1, α2, β, γ, and δ). The α1 subunit is also called the dihydropyridine receptor (DHPR) because it binds the dihydropyridine class of calcium channel–blocking drugs (e.g., nitrendipine and nimodipine). Although this channel complex is present in both skeletal and cardiac muscle, it serves very different functions in the two muscle types (discussed in the next paragraph).
In each cardiac muscle sarcomere, terminal regions of the SR abut T tubules and the sarcolemma (see