The Mechanism of Modulation of Cardiac Force by Temperature

Figures

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  Figure 1. Temperature dependence of isometric force and of the rate of force redevelopment. (A) Relation between isometric force at saturating [Ca2+], T0, and temperature. Open symbols = data from 6 trabeculae. Filled symbols = mean ± SEM, n = 2–6. (B) Superimposed sample records of force redevelopment following a large release from the steady isometric force at 10 (grey) and 30 °C (black). Force normalised for the steady value reached after the release. (C) Relation between rate of force redevelopment, kTR, measured by the reciprocal of the time to attain 63% of the redeveloped steady force and temperature. Data from the same six trabeculae as in (A). Symbols as in (A).

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  Figure 2. Protocol for measuring the half-sarcomere stiffness during isometric contraction at saturating [Ca2+]. (A) Force response (lower trace) to a train of length steps (% of the trabecula length, L0, upper trace), separated by 200 ms, imposed on the trabecula at the plateau of the isometric force developed at pCa 4.5. The horizontal line superimposed on the force response is the force baseline obtained with a large release (~7% of the initial trabecula length), imposed at the time marked by the vertical bar to drop the force to zero. The middle trace shows the half-sarcomere length change (nm/hs) recorded with the striation follower. Note that during the initial force development, there was a shortening of ~50 nm/hs against the end compliances. (B) Same traces as in (A) on a faster timescale and larger vertical amplification. Each step was followed after 50 ms by a step of the same amplitude in the opposite direction to recover the force and the sarcomere length before the next step. Half-sarcomere shortening/lengthening during the quick force recovery following a step release/stretch were accounted for by the end compliance. Force is expressed relative to the CSA in relaxing solution…

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  Figure 3. Stiffness and strain of the half-sarcomere in relation to the temperature-dependent changes in the isometric force. (A) Force (lower panel, with zero force shown by the bottom horizontal line) and change in the half-sarcomere length (upper panel) in response to a length step imposed on the isometric plateau of a trabecula activated at pCa 4.5, either at 10 °C (left) or at 25 °C (right). T1, the force attained at the end of the length step, is marked by the arrowhead. (B) T1 relations at 10 °C (filled circles) and at 25 °C (open circles). Solid and dashed lines are first-order regression equations fitted to the data at 10 and 25 °C, respectively. Data from the same trabecula as in Figure 2. (C) Relation of k0 versus the temperature-dependent isometric force. (D) Relation of Y0 versus the temperature-dependent isometric force. In (C,D): open circles, data from 6 trabeculae; filled circles, mean ± SEM (n = 2–6).

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  Figure 4. Mechanical model of the hs and dependence of half-sarcomere compliance (Chs) and the average strain of the attached motors (s0) on temperature-modulated T0. (A) Two-component model. Parameters identifying the compliance of the array of motors (1/(β·er) and the equivalent compliance of the filaments (Cf) defined in the text. (B) Dependence of Chs on T0. The continuous line is the first-order regression to the data points (filled symbols), calculated from the averaged data in Figure 3C. The slope is not significantly different from zero (p = 0.96), and the ordinate intercept is 65 ± 6 nm/MPa. The dashed line shows the contribution of Cf to Chs. (C) Dependence of s0 (left ordinate, calculated as detailed in the text) and the force per motor (F0; right ordinate, calculated as detailed in the text) on T0. The continuous line is the linear fit to data points and has an intercept not significantly different from the origin (p = 0.8). The dashed line shows the hs strain, from Figure 3D. Data are mean ± SEM from six trabeculae.

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  Figure 5. Relation between steady isometric force developed at pCa 4.5 and the reciprocal of absolute temperature Θ. Circles are mean ± SEM from Figure 1A. The line is the fit to the pooled data using (4).