Presentation Type
Oral/Paper Presentation
Abstract
Malignant Hyperthermia (MH) is a rare but potentially lethal pharmacogenetic disorder, affecting roughly 1 in 30,000 children and 1 in 100,000 adults undergoing surgery. MH can be triggered by agents used for general anesthesia. These may include volatile anesthetics such as sevoflurane, isoflurane, desflurane, halothane or depolarizing neuromuscular blockers such as succinylcholine. Upon administration of a trigger, an MH susceptible (MHS) patient can develop a hypermetabolic state during the intraoperative or postoperative periods. If not treated quickly, an MH episode could result in organ dysfunction or death. The primary mechanisms involved in the development of an MH crisis include the excitation-contraction coupling (ECC) mechanism, which functions to convert propagating action potentials at motor neurons to skeletal muscle contractions. Upon depolarization at the neuromuscular junction, action potentials propagate down T-Tubule invaginations where Ca2+ can then be released to initiate a muscle contraction. Regulation of this release is critical for maintaining Ca2+ homeostasis within a myofibril. Located within the muscle cell, the Ryanodine Type 1 Receptor (RYR1) is the primary protein involved in the release of intracellular Ca2+. Mutations in RYR1 can result in a gain of function activity, causing abnormally high levels of Ca2+ released into the myoplasmic region. Uncontrolled muscle contractions can then occur and further develop into the hypermetabolic state seen in MH. Current therapeutic and diagnostic measures for MH include Dantrolene sodium, which acts by inhibiting the activity of RYR1. Altogether, we argue that greater understanding and targeting of RYR1 could aid therapeutic interventions of MH.
Faculty Mentor
Dr. Josh Owens
Recommended Citation
Medina, Cesar and Owens, Joshua, "Functionality of the Ryanodine Receptor Type 1 (RyR1) in the Development of Malignant Hyperthermia (MH)" (2025). Student Scholar Symposium. 76.
https://digitalcollections.lipscomb.edu/student_scholars_symposium/2025/Full_schedule/76
Included in
Biology Commons, Cell Biology Commons, Medicine and Health Sciences Commons, Molecular Biology Commons
Functionality of the Ryanodine Receptor Type 1 (RyR1) in the Development of Malignant Hyperthermia (MH)
Malignant Hyperthermia (MH) is a rare but potentially lethal pharmacogenetic disorder, affecting roughly 1 in 30,000 children and 1 in 100,000 adults undergoing surgery. MH can be triggered by agents used for general anesthesia. These may include volatile anesthetics such as sevoflurane, isoflurane, desflurane, halothane or depolarizing neuromuscular blockers such as succinylcholine. Upon administration of a trigger, an MH susceptible (MHS) patient can develop a hypermetabolic state during the intraoperative or postoperative periods. If not treated quickly, an MH episode could result in organ dysfunction or death. The primary mechanisms involved in the development of an MH crisis include the excitation-contraction coupling (ECC) mechanism, which functions to convert propagating action potentials at motor neurons to skeletal muscle contractions. Upon depolarization at the neuromuscular junction, action potentials propagate down T-Tubule invaginations where Ca2+ can then be released to initiate a muscle contraction. Regulation of this release is critical for maintaining Ca2+ homeostasis within a myofibril. Located within the muscle cell, the Ryanodine Type 1 Receptor (RYR1) is the primary protein involved in the release of intracellular Ca2+. Mutations in RYR1 can result in a gain of function activity, causing abnormally high levels of Ca2+ released into the myoplasmic region. Uncontrolled muscle contractions can then occur and further develop into the hypermetabolic state seen in MH. Current therapeutic and diagnostic measures for MH include Dantrolene sodium, which acts by inhibiting the activity of RYR1. Altogether, we argue that greater understanding and targeting of RYR1 could aid therapeutic interventions of MH.