Abstract
An abnormality in myoplasmic Ca
2+ regulation has frequently been proposed in 20,25-diazacholesterol (20,25-D) myotonia. We report here the results of several studies of transmembrane Ca
2+ movement in this animal model. (i) Physiologic Ca
2+ release by intact sarcoplasmic reticulum (SR) was examined in chemically skinned single muscle fibers preloaded in EGTA-buffered Ca
2+ solutions (
pCa
2+ 7.0 to 6.4). Isometric tension development and Ca
2+ release thresholds in response to Cl
ā or caffeine showed no differences between control and 20,25-D fibers at any
pCa
2+. (ii) The kinetics of energy-dependent Ca
2+ accumulation in purified SR vesicles were followed spectrophotometrically using Ca
2+-sensitive dyes. The apparent rate for ATP-dependent Ca
2+ uptake and Ca
2+ sequestering capacity were unchanged in SR from 20,25-D animals vs. controls. (iii) Surface membrane Ca
2+ ATPase activity was measured in red blood cell ghosts and sarcolemma. Enzyme
V
max was decreased by 25 to 50% in both membranes in the 20,25-D-treated animals with a compensatory increase in the number of Ca
2+ ATPase molecules. In general, the SR handling of Ca
2+ appears normal in 20,25-D myotonia, although the activity of Ca
2+ ATPase in membranes with high sterol content may be altered in response to changes in the lipid environment in this model.