Figure 9

Molecular pathopysiology, action potentials and calcium transients in isolated myocytes of normal (A) vs. failing (B) hearts. Upper panels. Left: normal myocyte. Right: failing heart myocytes show depressed SERCA both in function, and in expression; the sarcolemmal sodium-calcium (Na⁺/Ca²⁺) exchanger is increased both in function and in expression, and correlates inversely with the SERCA levels. Lower panels: action potential and intracellular calcium transient. The action potentials recorded in myocytes isolated from the failing hearts (right) are markedly prolonged compared with that in a myocyte from a normal heart (control, left). The intracellular calcium transients measured with the fluorescent calcium indicator fura-2 are also markedly abnormal in myocytes isolated from the failing heart (right). Compared with a normal myocyte (control, left), the failing myocyte shows (plot s) an attenuated cytosolic Ca²⁺ rise with depolarization and a markedly delayed return to baseline. The intracellular calcium transient (plot d) from a myocyte with isolated diastolic dysfunction (normal cytolsolic Ca²⁺ systolic release, delayed cytosolic Ca²⁺ diastolic removal) shows a normal rise with depolarization and a markedly delayed return to baseline. These abnormalities reflect the altered expression or function of key calcium-handling proteins and contribute to the abnormal action potential in the top illustration. (Modified from: O'Rourke B, Kass DA, Tomaselli GF, et al. Mechanisms of altered excitation-contraction coupling in canine tachycardia-induced heart failure I. Circ Res 1999; 84: 562–70.)