Ryanodine receptor in different malignant hyperthermia-susceptible porcine muscles.
The sarcoplasmic reticulum (SR) ryanodine receptor was studied in SR vesicles isolated from the vastus intermedius skeletal muscle and cardiac muscle of malignant hyperthermia-susceptible (MHS) and normal pigs. MHS and normal heavy SR preparations isolated from the vastus intermedius muscle had similar yields, polyacrylamide gel electrophoretic patterns, Ca2(+)-ATPase activities, mitochondrial enzyme activities, calsequestrin contents, and maximal [3H]ryanodine-binding activities. However, while half-maximal calcium concentrations (Ca0.5) for stimulation of MHS and normal vastus intermedius SR [3H]ryanodine binding were not significantly different, the Ca0.5 for inhibition of [3H]ryanodine binding to MHS vastus intermedius SR (76 +/- 17 microM) was significantly greater than to normal SR (16 +/- 9 microM). MHS vastus intermedius SR also exhibited a significantly lower Kd value (62 +/- 15 nM) for [3H]ryanodine binding compared with normal SR (Kd = 284 +/- 102 nM). These values for MHS and normal vastus intermedius SR are similar to those reported using SR isolated from a muscle composed of predominantly fast-twitch fibers, indicating the similarity of the ryanodine receptor in fast- and slow-twitch skeletal muscles. In contrast, there were no differences in the properties of the ryanodine receptor of porcine cardiac SR isolated from MHS and normal pigs. We therefore conclude that there is a defect in the SR ryanodine receptor of both slow- and fast-twitch skeletal muscle fiber types but not in cardiac muscle of MHS individuals.
Ervasti
J M
JM
Department of Biochemistry, University of Minnesota, St. Paul 55108.
Strand
M A
MA
Hanson
T P
TP
Mickelson
J R
JR
Louis
C F
CF
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D004198:Disease Susceptibility; D015151:Immunoblotting; D008305:Malignant Hyperthermia / Q000378:metabolism*; D008970:Molecular Weight; D009124:Muscle Proteins / Q000378:metabolism; D009132:Muscles / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D012433:Ryanodine / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D013552:Swine
D009124:Muscle Proteins; D011950:Receptors, Cholinergic; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D000252:Calcium-Transporting ATPases; D002118:Calcium