Physiological determinants of contractile force generation and calcium handling in mouse myocardium.
Despite the fact that the mouse has become a common tool to study cardiac dysfunction, little is known regarding the regulation of murine cardiac contractility. We have investigated the three main mechanisms that regulate cardiac output (frequency-dependent activation, length-dependent activation, and beta-adrenergic stimulation) in ultra-thin right ventricular (RV) trabeculae from the mouse heart at body temperature (37 degrees C). [Ca(2+)](i) was recorded in a subset of trabeculae iontophoretically loaded with fura-2, and rapid cooling contractures were performed to estimate the sarcoplasmic reticulum (SR) calcium load. The force-frequency relationship was positive (2-12Hz); force increased, albeit slightly, while relaxation timing decreased. As expected, in response to beta-adrenergic stimulation, force development increased while contractile duration decreased, and increased muscle length led to increased force generation. Changes in SR calcium load and the calcium transient amplitude paralleled effects on active force generation. Despite several qualitative similarities with other mammalian species, the reserve for augmentation of force via either increased frequency or beta-adrenergic stimulation was considerably smaller in mouse than in other animals. Therefore, changes in preload, as opposed to increased HR or adrenergic tone, appears to be a much more important determinant of cardiac performance in the mouse than in larger mammals.
Stull
Linda B
LB
The Institute of Molecular Cardiobiology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
Leppo
Michelle K
MK
Marbán
Eduardo
E
Janssen
Paul M L
PM
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004558:Electric Stimulation; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013268:Stimulation, Chemical; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D007545:Isoproterenol; D002118:Calcium