Transmembrane calcium movement in 20,25-diazacholesterol myotonia.
An abnormality in myoplasmic Ca2+ regulation has frequently been proposed in 20,25-diazacholesterol (20,25-D) myotonia. We report here the results of several studies of transmembrane Ca2+ movement in this animal model. (i) Physiologic Ca2+ release by intact sarcoplasmic reticulum (SR) was examined in chemically skinned single muscle fibers preloaded in EGTA-buffered Ca2+ solutions (pCa2+7.0 to 6.4). Isometric tension development and Ca2+ release thresholds in response to Cl- or caffeine showed no differences between control and 20,25-D fibers at any pCa2+. (ii) The kinetics of energy-dependent Ca2+ accumulation in purified SR vesicles were followed spectrophotometrically using Ca2+-sensitive dyes. The apparent rate for ATP-dependent Ca2+ uptake and Ca2+ sequestering capacity were unchanged in SR from 20,25-D animals vs. controls. (iii) Surface membrane Ca2+ATPase activity was measured in red blood cell ghosts and sarcolemma. Enzyme Vmax was decreased by 25 to 50% in both membranes in the 20,25-D-treated animals with a compensatory increase in the number of Ca2+ATPase molecules. In general, the SR handling of Ca2+ appears normal in 20,25-D myotonia, although the activity of Ca2+ATPase in membranes with high sterol content may be altered in response to changes in the lipid environment in this model.
Mollman
J E
JE
Furman
R E
RE
Wood
D S
DS
Scarpa
A
A
Barchi
R L
RL
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001373:Azacosterol; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002712:Chlorides / Q000494:pharmacology; D002784:Cholesterol / Q000031:analogs & derivatives; D004533:Egtazic Acid / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000201:enzymology; D007700:Kinetics; D008297:Male; D009222:Myotonia / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012508:Sarcolemma / Q000201:enzymology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D002712:Chlorides; D002110:Caffeine; D004533:Egtazic Acid; D000255:Adenosine Triphosphate; D002784:Cholesterol; D000252:Calcium-Transporting ATPases; D001373:Azacosterol; D002118:Calcium