Ca2+ increases cardiac muscle viscoelasticity independent of active force development

Abstract

In addition to activation of muscle contraction by Ca2+, recent studies suggest that Ca2+ also affects muscle passive mechanical properties. The goal of this study was to determine if Ca2+ regulates the stiffness of cardiac muscle, independent of active contraction. The mechanical response to stretch for mouse demembranated cardiac trabeculae was probed at different Ca2+ levels after eliminating active contraction using a combination of two myosin ATPase inhibitors: para-nitroblebbistatin (PNB, 50 M), plus mavacampten (Mava, 50 M). Myocardial force level was assessed during large stretches ({asymp} 20% initial muscle length) with a range of stretch velocities. For relaxed muscle, in response to stretch, muscle force rose to a peak and then decayed toward a lower steady-state level, consistent with the viscoelastic nature of cardiac muscle. Peak force was higher with faster stretch velocity, but the steady-state force was independent of stretch velocity, consistent with the presence of both apparent viscous and elastic components of the stretch response. In the presence of the inhibitors PNB plus Mava, when Ca2+ level was increased, active contraction was completely prevented. However, the viscoelastic force response to stretch was markedly increased by high Ca2+ and was > 6-fold higher than at low Ca2+ level. The relationship of viscous force to Ca2+ level had a similar form to the relationship of active force to Ca2+ (measured in the absence of inhibitors), suggesting a common regulatory mechanism is involved. As expected, Ca2+-activated contraction was inhibited by lowering the temperature from 21{degrees}C to 10{degrees}C. In contrast, the Ca2+-activated viscous property was not inhibited at lower temperature, further suggesting that active contraction and the viscous property involve distinct mechanisms. This study demonstrates that in addition to triggering activation of contraction, Ca2+ also increases the apparent viscous property of cardiac muscle. New and NoteworthyCa2+ is well-known to trigger activation of muscle contraction. This study demonstrates a new mechanical role for Ca2+ in cardiac muscle involving a >6-fold increase in the apparent muscle viscoelasticity. Activation of a viscous element by Ca2+ might influence the mechanical properties of activated cardiac muscle.