Action potential characterization in intact mouse heart: steady-state cycle length dependence and electrical restitution.
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, APD(30) reached plateau values significantly faster than APD(90) (tau = 29 +/- 2 vs. 78 +/- 6 ms, P < 0.01, n = 12). The slope of early APD(90) 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 Ca(2+) transients recorded from isolated ventricular myocytes at 37 degrees C (tau = 93 +/- 4 ms, n = 18) resembled the APD(90) 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.
Knollmann
Björn C
BC
Oates Institute for Experimental Therapeutics, Vanderbilt Univ. School of Medicine, Division of Clinical Pharmacology, 1265 Medical Research Bldg. IV, Nashville, TN 37232-0575, USA. bjorn.knollmann@vanderbilt.edu
Schober
Tilmann
T
Petersen
Andreas O
AO
Sirenko
Syevda G
SG
Franz
Michael R
MR
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D016279:Atrial Function, Left / Q000502:physiology*; D001683:Biological Clocks / Q000502:physiology*; D002478:Cells, Cultured; D004558:Electric Stimulation; D004562:Electrocardiography; D006329:Heart Conduction System / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D032383:Myocytes, Cardiac / Q000502:physiology*; D012032:Refractory Period, Electrophysiological / Q000502:physiology*; D016276:Ventricular Function