Volatile anesthetics inhibit dihydropyridine binding to malignant hyperthermia-susceptible and normal pig skeletal muscle membranes.
BACKGROUND
Surface membrane dihydropyridine receptor Ca2+ channels may play a role in the response of malignant hyperthermia-susceptible skeletal muscle to volatile anesthetics.


METHODS
We determined the effect of halothane, enflurane, and isoflurane on the binding of the Ca2+ channel blocker PN200-110 to skeletal muscle membranes isolated from malignant hyperthermia-susceptible and normal pigs.


RESULTS
In the presence of 0.4 mM halothane, the maximal [3H]PN200-110 binding to both normal and malignant hyperthermia membranes was reduced by 37-43% (P < 0.05). There was no difference in the equilibrium constant for the halothane-dependent inhibition of [3H]PN200-110 binding to these two types of membranes. There also was no significant difference among halothane, enflurane, or isoflurane in their ability to inhibit [3H]PN200-110 binding to either normal or malignant hyperthermia membranes.


CONCLUSIONS
Volatile anesthetics inhibit the binding of PN200-110 to skeletal muscle membranes by decreasing the number of functionally active dihydropyridine receptor proteins. This inhibition is similar for membranes isolated from both normal and malignant hyperthermia-susceptible muscle, thus providing no evidence for a halothane-induced functional defect in this protein in malignant hyperthermia-susceptible muscle. However, the results of this study also indicate that the mechanism by which volatile anesthetics decrease surface membrane Ca2+ currents in skeletal muscle is by reducing the number of functional dihydropyridine receptor Ca2+ channels.
Louis
C F
CF
Department of Veterinary PathoBiology, University of Minnesota, St. Paul 55108.
Roghair
T
T
Mickelson
J R
JR
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004347:Drug Interactions; D006221:Halothane / Q000494:pharmacology; D017275:Isradipine / Q000378:metabolism; D008305:Malignant Hyperthermia / Q000235:genetics / Q000378:metabolism*; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009124:Muscle Proteins / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism*; D013552:Swine; D014316:Tritium
D000777:Anesthetics; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; D009124:Muscle Proteins; D014316:Tritium; D006221:Halothane; D017275:Isradipine