Effect of Norepinephrine on Intracellular Ca2+ Levels in Malignant Hyperthermia-Susceptible B Cells: Pilot Study in the Search for a New Diagnostic Test for Malignant Hyperthermia.

Malignant hyperthermia (MH) crises may induce morbidity or death in MH-susceptible (MHS) individuals. The only sensitive method of determining susceptibility is the caffeine-halothane contracture test, requiring muscle biopsy. Early research on MH demonstrated an abnormal response to catecholamines in MHS individuals. The purpose of this study was to determine whether MHS B lymphocytes would demonstrate an increased sensitivity to norepinephrine as indicated by an adrenergic augmentation of intracellular calcium ion (Ca²⁺) accumulation, to possibly develop a less invasive laboratory assay for determining MH susceptibility. The fluorescent Ca²⁺ indicator dye fura-2 acetoxymethyl was used to identify Ca²⁺ flux within Epstein-Barr virus- immortalized MH-negative (MHN) and MHS B cells exposed to the RyR1 agonist 4-chloro-m-cresol (4-CmC) before and after administration of 1 μM of norepinephrine. In the presence of 4-CmC and norepinephrine, the area under the curve dose responses were significantly elevated in MHS B cells compared with MHN B cells (F[1,10] = 27.37; P < .01). Epstein-Barr virus-immortalized B cells from MHS humans displayed an increased sensitivity to norepinephrine compared with those from MHN individuals. These data suggest that an abnormal response to exogenous norepinephrine could potentially be used to develop a diagnostic laboratory assay to determine MH susceptibility.