title: Myofilament properties comprise the rate-limiting step for cardiac relaxation at body temperature in the rat.
abstract: The majority of studies aimed at characterizing basic contractile mechanisms have been conducted at room temperature. To elucidate the mechanism of cardiac relaxation under more physiological conditions, we investigated contractile function and calcium handling in ultrathin rat cardiac trabeculae. Active developed tension was unaltered between 22.5 and 30.0 degrees C (from 89 +/- 10 to 86 +/- 11 mN/mm(2), P = not significant) but steeply declined at 37.5 degrees C (30 +/- 5 mN/mm(2)). Meanwhile, the speed of relaxation (time from peak force to 50% relaxation) declined from 22.5 to 30.0 degrees C (from 360 +/- 40 to 157 +/- 17 ms) and further declined at 37.5 degrees C to 76 +/- 13 ms. Phase-plane analysis of calcium versus force revealed that, with increasing temperature, the relaxation phase is shifted rightward, indicating that the rate-limiting step of relaxation tends to depend more on calcium kinetics as temperature rises. The force-frequency relationship, which was slightly negative at 22.5 degrees C (0.1 vs. 1 Hz: 77 +/- 12 vs. 66 +/- 7 mN/mm(2)), became clearly positive at 37.5 degrees C (1 vs. 10 Hz: 30 +/- 5 vs. 69 +/- 9 mN/mm(2)). Phase-plane analyses indicated that, with increasing frequency, the relaxation phase is shifted leftward. We conclude that temperature independently affects contraction and relaxation, and cross-bridge cycling kinetics become rate limiting for cardiac relaxation under experimental conditions closest to those in vivo.
authors.affiliation: Institute of Molecular Cardiobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. pjanssen@jhmi.edu
authors.forename: Paul M L
authors.initials: PM
authors.lastname: Janssen
authors.forename: Linda B
authors.initials: LB
authors.lastname: Stull
authors.forename: Eduardo
authors.initials: E
authors.lastname: Marbán
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology*; D000818:Animals; D001831:Body Temperature / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D004558:Electric Stimulation; D016257:Fura-2 / Q000494:pharmacology; D066298:In Vitro Techniques; D007478:Iontophoresis; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000166:cytology; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D002614:Chelating Agents; D002118:Calcium; D016257:Fura-2