Acidosis or inorganic phosphate enhances the length dependence of tension in rat skinned cardiac muscle

1. We investigated the effect of acidosis on the sarcomere length (SL) depe ndence of tension generation, in comparison with the effect of inorganic ph osphate (P-i), in rat skinned ventricular trabeculae. The shift of the mid- point of the pCa-tension relationship associated with an increase in SL fro m 1.9 to 2.3 mum (Delta pCa(50)) was studied. 2. Decreasing pH from 7.0 to 6.2 lowered maximal and submaximal Ca2+-activa ted tension and increased Delta pCa(50), in a pH-dependent manner (from 0.2 1 +/- 0.01 to 0.30 +/- 0.01 pCa units). The addition of P-i (20 mM) decreas ed maximal tension and enhanced the SL dependence, both to a similar degree as observed when decreasing pH to 6.2 (Delta pCa(50) increased from 0.20 /- 0.01 to 0.29 +/- 0.01 pCa units). 3. Further experiments were performed using 6% (w/v) Dextran T-500 (molecul ar weight similar to 500 000) to osmotically reduce interfilament lattice s pacing (SL, 1.9 mum). Compared with that at pH 7.0, in the absence of P-i t he increase in the Ca2+ sensitivity of tension induced by osmotic compressi on was enhanced at pH 6.2 (0.18 +/- 0.01 vs. 0.25 +/- 0.01 pCa units) or in the presence of 20 mM P-i (0.17 +/- 0.01 vs. 0.24 +/- 0.01 pCa units). 4. H+, as well as P-i, has been reported to decrease the number of strongly binding cross-bridges, which reduces the co-operative activation of the th in filament, and increases the pool of detached cross-bridges available for interaction with actin. It is therefore considered that during acidosis, t he degree of increase in the number of force-generating cross-bridges upon reduction of interfilament, lattice spacing is enhanced, resulting in great er SL dependence of tension generation. 5. Our results suggest that the Fra nk-Starling mechanism may be enhanced when tension development is suppresse d due to increased H+ and/or P-i under conditions of myocardial ischaemia o r hypoxia.