SASAKI Daisuke    Department   Research Institutes and Facilities, Research Institutes and Facilities    Position   Assistant Professor (Fixed Term)
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Acidosis or inorganic phosphate enhances the length dependence of tension in rat skinned cardiac muscle.
Journal	Formal name：The Journal of physiology Abbreviation：J Physiol ISSN code：00223751/00223751
Domestic / Foregin	Foregin
Volume, Issue, Page	536(Pt 1),pp.153-60
Author and coauthor	Fukuda N, O-Uchi J, Sasaki D, Kajiwara H, Ishiwata S, Kurihara S
Publication date	2001/10
Summary	1. We investigated the effect of acidosis on the sarcomere length (SL) dependence of tension generation, in comparison with the effect of inorganic phosphate (P(i)), in rat skinned ventricular trabeculae. The shift of the mid-point of the pCa-tension relationship associated with an increase in SL from 1.9 to 2.3 microm (DeltapCa(50)) was studied. 2. Decreasing pH from 7.0 to 6.2 lowered maximal and submaximal Ca(2+)-activated tension and increased DeltapCa(50) in a pH-dependent manner (from 0.21 +/- 0.01 to 0.30 +/- 0.01 pCa units). The addition of P(i) (20 mM) decreased maximal tension and enhanced the SL dependence, both to a similar degree as observed when decreasing pH to 6.2 (DeltapCa(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 (molecular weight approximately 500 000) to osmotically reduce interfilament lattice spacing (SL, 1.9 microm). Compared with that at pH 7.0, in the absence of P(i) the increase in the Ca(2+) sensitivity of tension induced by osmotic compression 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 thin filament and increases the pool of detached cross-bridges available for interaction with actin. It is therefore considered that during acidosis, the degree of increase in the number of force-generating cross-bridges upon reduction of interfilament lattice spacing is enhanced, resulting in greater SL dependence of tension generation. 5. Our results suggest that the Frank-Starling mechanism may be enhanced when tension development is suppressed due to increased H(+) and/or P(i) under conditions of myocardial ischaemia or hypoxia.
DOI	10.1111/j.1469-7793.2001.00153.x
PMID	11579165