Differences between mouse and rat myocardial contractile responsiveness tocalcium

Genetically altered mice have become an increasingly important tool for the study of mechanisms of cardiac function, and therefore it is vital to char acterize the basic contractile properties of the mouse heart. As a first ap proach to this goal, we first optimized perfusion conditions and characteri zed the effect of incremental left ventricular balloon inflation on end-dia stolic, systolic and developed pressures in the isovolumically-contracting mouse heart. Under constant loading conditions, we determined developed pre ssure in response to changing perfusate calcium (1.25, 2.5, 3.75 and 5.0 mM ) and perfusate temperature (30 and 37 degrees C). We then compared the int rinsic inotropic responsiveness to changes in extracellular calcium of left ventricular myocardium from mouse to that from the rat. In the baseline st ate (1.25 mM extracellular calcium; [Ca2+](o)), both isometric contraction duration and normalized active force at the peak of the active force-length relationship (L-max) were less in mouse than in rat myocardium. Under isot onic conditions, temporal parameters of shortening and the relative shorten ing were less in mouse vs rat myocardium. Increasing [Ca2+](o) from 1.25 to 2.5 mM markedly increased active isometric force and rate of force develop ment (+ dF/dt) in the mouse. However, rat myocardium responded to a lesser extent. Under isotonic conditions, peak shortening and the rate of shorteni ng also increased to a greater extent in mouse relative to rat myocardium. Increasing the bath calcium concentration to 5.0 mM increased isometric for ce and + dF/dt further in the rat but not the mouse, suggesting that two sp ecies operate at different points on the force vs [Ca2+](o) relationship. W e conclude that mouse myocardium exhibits increased sensitivity to changes in [Ca2+](o) within the physiologic range in comparison to rat. These diffe rences do not appear to be due to differences in loading conditions. The da ta suggest that differences in inotropic responsiveness to calcium may refl ect intrinsic differences in myocardial calcium sensitivity between species . (C) 1999 Elsevier Science Inc. All rights reserved.