Altered E-C coupling in triads isolated from malignant hyperthermia-susceptible porcine muscle.
Triad vesicles were isolated from normal (N) and homozygous malignant hyperthermia-susceptible (MHS) porcine skeletal muscle, and two types of sarcoplasmic reticulum Ca2+ release were investigated: 1) polylysine-induced Ca2+ release (direct stimulation of the junctional foot protein), and 2) depolarization-induced Ca2+ release (stimulation of the junctional foot protein via the dihydropyridine receptor). At submaximal concentrations of polylysine, the rates of induced Ca2+ release from the MHS triads were greater than from normal triads. The T tubules of polarized triads were depolarized by the K(+)-to-Na+ ionic replacement protocol. Higher grades of T-tubule depolarization resulted in higher rates of Ca2+ release from both MHS and normal triads but, when compared at a given grade of T-tubule depolarization, the release rate was always greater from the MHS than from normal triads. Thus the activity of the SR Ca2+ release channel is always higher in MHS than in normal muscle at a given submaximal dose of release trigger. This difference is observed when the channel is stimulated directly by polylysine or indirectly via a depolarization-induced activation of the T-tubule dihydropyridine receptor.
el-Hayek
R
R
Department of Veterinary Biology, University of Minnesota, St. Paul 55108, USA.
Yano
M
M
Antoniu
B
B
Mickelson
J R
JR
Louis
C F
CF
Ikemoto
N
N
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004198:Disease Susceptibility; D007700:Kinetics; D008305:Malignant Hyperthermia / Q000503:physiopathology / Q000662:veterinary*; D008564:Membrane Potentials; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000502:physiology* / Q000503:physiopathology*; D011107:Polylysine / Q000494:pharmacology; D012016:Reference Values; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D013552:Swine; D013553:Swine Diseases; D013997:Time Factors
D011107:Polylysine; D002118:Calcium