TRPV1 variants impair intracellular Ca²⁺ signaling and may confer susceptibility to malignant hyperthermia.

ABSTRACT:

Purpose

Malignant hyperthermia (MH) is a pharmacogenetic disorder arising from uncontrolled muscle calcium release due to an abnormality in the sarcoplasmic reticulum (SR) calcium-release mechanism triggered by halogenated inhalational anesthetics. However, the molecular mechanisms involved are still incomplete.

Methods

We aimed to identify transient receptor potential vanilloid 1 (TRPV1) variants within the entire coding sequence in patients who developed sensitivity to MH of unknown etiology. In vitro and in vivo functional studies were performed in heterologous expression system, trpv1^-/- mice, and a murine model of human MH.

Results

We identified TRPV1 variants in two patients and their heterologous expression in muscles of trpv1^-/- mice stro

SUBMITTER: Vanden Abeele F 

PROVIDER: S-EPMC6752298 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature