Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 292, Issue 1, Pages H614-H621Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.01085.2005
Keywords
atrium; ventricle; monophasic action potential; calcium transients
Funding
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL071670] Funding Source: NIH RePORTER
- NHLBI NIH HHS [R01 HL-71670] Funding Source: Medline
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Transgenic mice have been increasingly utilized to investigate the molecular mechanisms of cardiac arrhythmias, yet the rate dependence of the murine action potential duration and the electrical restitution curve (ERC) remain undefined. In the present study, 21 isolated, Langendorff-perfused, and atrioventricular node-ablated mouse hearts were studied. Left ventricular and left atrial action potentials were recorded using a validated miniaturized monophasic action potential probe. Murine action potentials (AP) were measured at 30, 50, 70, and 90% repolarization (APD(30)-APD(90)) during steady-state pacing and varied coupling intervals to determine ERCs. Murine APD showed rate adaptation as well as restitution properties. The ERC time course differed dramatically between early and late repolarization: APD(30) shortened with increasing S1-S2 intervals, whereas APD(90) was prolonged. When fitted with a monoexponential function, APD30 reached plateau values significantly faster than APD90 (tau = 29 +/- 2 vs. 78 +/- 6 ms, P < 0.01, n = 12). The slope of early APD90 restitution was significantly < 1 (0.16 +/- 0.02). Atrial myocardium had shorter final repolarization and significantly faster ERCs that were shifted leftward compared with ventricular myocardium. Recovery kinetics of intracellular Ca2+ transients recorded from isolated ventricular myocytes at 37 degrees C (tau = 93 +/- 4 ms, n = 18) resembled the APD90 ERC kinetics. We conclude that mouse myocardium shows AP cycle length dependence and electrical restitution properties that are surprisingly similar to those of larger mammals and humans.
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