Porcine malignant hyperthermia susceptibility: halothane-induced increase in cytoplasmic free calcium in lymphocytes.
We tested the hypothesis that lymphocytes from swine with susceptibility to malignant hyperthermia (MH) had increased sensitivity to the membrane-perturbing effects of halothane that increase cytoplasmic calcium. Cytoplasmic concentration of ionized calcium in lymphocytes isolated from blood was determined in the presence and absence of halothane for 10 Pietrain x Poland China swine that were susceptible to MH and 20 Yorkshire swine that were resistant to MH. Calcium was determined by dual-emission spectrofluorometry and by measuring the ratio of free to calcium-bound form of the fluorescent calcium dye Indo-1. Mean values for calcium concentrations in lymphocytes from MH-susceptible (MHS) swine were 80% less than control values (40.5 +/- 38.8 and 185.3 +/- 91.6 nmol/L; P less than 0.01). Untreated lymphocytes from MHS swine accumulated calcium at half the rate observed for controls. Exposure to 1 mmol/L halothane resulted in a 3-fold increase of free calcium concentration to 127.9 +/- 81.3 nmol/L in the lymphocytes of MHS swine, but had no significant effect on lymphocytes from control swine (225.0 +/- 91.4; P less than 0.01). Exposure to 2 mmol/L halothane resulted in a 6-fold increase of free calcium concentration to 255.9 +/- 91.4 nmol/L in lymphocytes from MHS swine and a 63% increase in lymphocytes from controls (303.8 +/- 116). The rate of halothane-induced increase in cytosolic calcium was 13 times greater in lymphocytes from MHS swine, compared with controls. These data indicated that the molecular defect that results in halothane-hypersensitivity and is characteristic of muscle of MHS swine also occurs in lymphocytes from MHS swine.
O'Brien
P J
PJ
Department of Pathology, Ontario Veterinary College, University of Guelph, Canada.
Kalow
B I
BI
Brown
B D
BD
Lumsden
J H
JH
Jacobs
R M
RM
D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D003600:Cytosol / Q000032:analysis / Q000378:metabolism; D004198:Disease Susceptibility; D006221:Halothane / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008305:Malignant Hyperthermia / Q000097:blood / Q000175:diagnosis / Q000662:veterinary*; D013050:Spectrometry, Fluorescence; D013552:Swine; D013553:Swine Diseases / Q000097:blood*
D002118:Calcium; D006221:Halothane