Slow calcium current is not reduced in malignant hyperthermic porcine myotubes.
Malignant hyperthermia-susceptible (MHS) pigs express a sarcoplasmic reticulum (SR) Ca(2)+-release channel mutation that results in lower than normal contractile thresholds in skeletal muscles. In adult MHS pig muscles the L-type calcium current (ls) is also reduced. We tested the hypothesis that there is a causal relationship between ls and the lower contractile threshold by recording ls from MHS and normal porcine myotubes using the whole cell patch-clamp technique. Current voltage relationships for both MHS and normal myotubes were similar, with peak ls between +20 and +30 mV. Maximum ls amplitudes were not different from (normal: 4976 +/- 566 pA; MHS:6516 +/- 1088 pA) nor was ls specific density (normal: 9.0 +/- 0.8; MHS: 8.8 +/- 1.1 pA/pF). In both MHS and normal myotubes, both the dihydropyridine antagonist PN200-110 (200 nmol/L) and holding the membrane potential at -10mV for 5 min decreased ls significantly (by more than 50%). There was no apparent direct relationship between the mutation in the SR Ca(2)+ -release channel mutation on muscle development.
Gallant
E M
EM
Department of Veterinary PathoBiologoy, University of Minnesota, St. Paul, USA.
Balog
E M
EM
Beam
K G
KG
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000494:pharmacology; D008305:Malignant Hyperthermia / Q000473:pathology / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology*; D012016:Reference Values; D013552:Swine
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D002118:Calcium