TY - JOUR
T1 - Physiological determinants of contractile force generation and calcium handling in mouse myocardium
AU - Stull, Linda B.
AU - Leppo, Michelle K.
AU - Marbán, Eduardo
AU - Janssen, Paul M L
PY - 2002/10/1
Y1 - 2002/10/1
N2 - 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 β-adrenergic stimulation) in ultra-thin right ventricular (RV) trabeculae from the mouse heart at body temperature (37°C). [Ca2+]1 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 (2-12 Hz); force increased, albeit slightly, while relaxation timing decreased. As expected, in response to β-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 β-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.
AB - 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 β-adrenergic stimulation) in ultra-thin right ventricular (RV) trabeculae from the mouse heart at body temperature (37°C). [Ca2+]1 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 (2-12 Hz); force increased, albeit slightly, while relaxation timing decreased. As expected, in response to β-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 β-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.
KW - Calcium
KW - Cardiac
KW - Contractility
KW - Mice
KW - Ventricular trabeculae
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U2 - 10.1016/S0022-2828(02)92065-1
DO - 10.1016/S0022-2828(02)92065-1
M3 - Article
C2 - 12392997
AN - SCOPUS:0036772442
SN - 0022-2828
VL - 34
SP - 1367
EP - 1376
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
IS - 10
ER -