The Effects of Volatile Anesthetics on Calcium Regulation by-Malignant Hyperthermia—Susceptible Sarcoplasmic Reticulum
| Autor: | Timothy J. Roghair, Kristine Zualkernan, Charles F. Louis, James R. Mickelson |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Swine
chemistry.chemical_element In Vitro Techniques Calcium Enflurane medicine Animals Calcium metabolism Isoflurane business.industry Endoplasmic reticulum Malignant hyperthermia musculoskeletal system medicine.disease Sarcoplasmic Reticulum Anesthesiology and Pain Medicine chemistry Anesthesia Anesthetic Biophysics Disease Susceptibility Halothane Malignant Hyperthermia business medicine.drug |
| Zdroj: | Anesthesiology. 77:114-125 |
| ISSN: | 0003-3022 |
| DOI: | 10.1097/00000542-199207000-00017 |
| Popis: | To clarify the mechanism by which volatile anesthetics initiate malignant hyperthermia (MH), we examined the effect of halothane, isoflurane, and enflurane on Ca2+ uptake and release by sarcoplasmic reticulum vesicles isolated from MH-susceptible (MHS) and normal pig muscle. Clinical concentrations of these anesthetics (0.1-0.5 mM) stimulated sarcoplasmic reticulum ATP-dependent Ca2+ uptake (maximal at approximately 4 mM), whereas 10-20 times the clinical anesthetic concentration inhibited Ca2+ uptake. There was no significant difference between MHS and normal sarcoplasmic reticulum in any aspect of Ca2+ uptake. Ca2+ release from 45Ca(2+)-filled sarcoplasmic reticulum vesicles in a 10(-8) M Ca(2+)-containing medium (pH 7.0) was significantly stimulated at clinical concentrations of all three volatile anesthetics (anesthetic concentration for the 50% stimulation of Ca2+ release = 0.096-0.22 mM); however, the rate constant for Ca2+ release from MHS sarcoplasmic reticulum was in all cases significantly greater than that from normal sarcoplasmic reticulum. Furthermore, 0.5 mM halothane had no effect on Ca2+ release from normal sarcoplasmic reticulum at pH values less than 6.8, although it could still significantly stimulate Ca2+ release from MHS sarcoplasmic reticulum even at pH 6.4; similar results were obtained for isoflurane and enflurane. These studies thus demonstrate that the interaction of volatile anesthetics with the sarcoplasmic reticulum Ca(2+)-release channel is altered in MHS porcine muscle such that the channel may be activated even at a Ca2+ concentration or pH that would be expected to maintain the channel in the closed state. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|