Pathophysiological Role of Trpv1 In Malignant Hyperthermia: Identification of New Variants

Nolwenn Tessier¹#, Mallory Ducrozet¹#, Sylvie Ducreux¹, Julien Faure*² and Fabien Van Coppenolle*¹

Received: November 24, 2018;   Published: December 11, 2018

DOI: 10.26717/BJSTR.2018.12.002181

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Abstract

Malignant hyperthermia is a pharmacogenetic disorder caused by volatile anesthetics that trigger severe muscle contraction and a hypermetabolic state. Outside triggered crisis, patients are asymptomatic. The molecular mechanisms of MH involve an uncontrolled increase of cytosolic Ca2+ concentration in skeletal muscles, which contributes to excessive muscle contraction and rigidity, increased body temperature, severe rhabdomyolysis and a generalized acidosis and hypermetabolic state. Mutations altering the function of the 2 main calcium channels involved in muscle contraction were so far linked to Malignant Hyperthermia. Recently, we showed that mutations in the Transient Receptor Potential Vanilloid 1 (TRPV1) cation channel could also be involved in MH. We propose that TRPV1, acting as a Ca2+ leak channel, is a target of volatile anesthetics such as isoflurane as well as a mechanism that could explain its implication in MH.

Abbreviations : MH: Malignant Hyperthermia; TRPV1: Transient Receptor Potential Vanilloid 1; RyR1: Ryanodine Receptor type 1; Ca2+: Calcium