ISSN:
1435-1803
Keywords:
phosphate
;
humancardiac skinned fibers
;
myofibrillarcalcium sensitivity
;
ATPase activity
;
hypoxia
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary During hypoxic heart failure, inorganic phosphate (Pi) accumulates. We report the effects of Pi on force development and on myofibrillar ATPase-activity of human skinned atrial fibers, both at normal and at reduced levels of Mg-ATP. Pi (10 mM) depressed force production at maximal calcium activation (pCa 4.3) by about 40%. At higher pCa values (pCa 5.6), foree inhibition was even more pronounced, but at low concentrations of Mg-ATP (10 μM), Pi was less effective. In contrast to contractile force, myofibrillar ATPase was only inhibited by about 10% at pCa 4.3, whereas it could be inhibited by 40–50% at submaximal calcium activation (pCa 5.6). As Pi inhibited contractile force more than ATPase activity, the ratio of ATPase-activity to foree (tension cost) was increased by inorganic phosphate. ATPase-activity and tension cost were significantly reduced by loweing Mg-ATP concentration to 10 μM, whereas contractile force was less affected. Pi did not affect ATPase under these conditions at 10 mM Mg-ATP. Pi also shifted the calcium-force relationship towards higher Ca++ concentrations, that is, it decreased calcium sensitivity. In contrast, the calcium sensitivity of myofibrillar ATPase was less affected. These findings suggest that inorganic phosphate may affect the myocardium by altering crossbridge kinetics rather than the calcium affinity of troponin-C. Because of its inhibitory effect on myofibrillar ATPase, inorganic phosphate may be partly cardioprotective in the hypoxic myocardium. However, this “energy sparing” effect is probably offset by the greater “tension cost” that decreases the “efficiency” of tension maintenance in the presence of inorganic phosphate.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01907128
Permalink
