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Patomecanismo das mutações do recetor rianodina e a sua implicação na Hipertemia Maligna: Revisão da literatura
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| Documento em Acesso Embargado até dia 28-01-2026. Tente solicitar cópia ao autor carregando no ficheiro | 1.5 MB | Adobe PDF |
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Abstract(s)
Introdução: a hipertermia maligna (HM) é uma perturbação farmacogenética autossómica dominante que envolve o músculo esquelético. A mutação associada envolve o recetor rianodina (RyR), nomeadamente a isoforma 1, ao nível do retículo sarcoplasmático (RS). Estas mutações vão provocar um aumento exacerbado na concentração de cálcio intraplasmático, ativando os processos bioquímicos relacionados com a ativação muscular, que vão levar às alterações fisiopatológicas da HM. Objetivos: pretende-se com este trabalho elaborar uma revisão bibliográfica sobre o papel da isoforma 1 do recetor rianodiana (RyR1) na HM, sendo o objetivo principal, descrever o mecanismo de ação do RyR1 e a sua implicação na patologia. Metodologia: foi realizada uma pesquisa na base de dados eletrónica Pubmed®, considerando apenas artigos escritos em inglês e sem restrições quanto à região e ano de publicação. A data da última pesquisa foi 20 de dezembro de 2024. Apenas foram selecionados artigos que abordassem o patomecanismo da doença ou que identificassem possíveis mutações novas do recetor. Previamente à pesquisa, foram definidas as palavras-chave: RyR1, patomecanismo, hipertermia maligna, mutações e canalopatias. Conclusões: as mutações no recetor RyR1 resultam numa fuga constante de cálcio em repouso, num acoplamento defeituoso da contração de excitação e num aumento do stress oxidativo mitocondrial. Estas mutações alteram a cinética do canal e o tornam-no hipersensível a ligantes ativadores de canal, como a cafeína e o halotano.
Introduction: malignant hyperthermia is an autosomal dominant pharmacogenetic disorder affecting skeletal muscle. The associated mutation involves the ryanodine receptor, namely isoform 1 at the level of the sarcoplasmic reticulum. These mutations cause an exaggerated increase in plasma intra calcium concentration, activating biochemical processes related to muscle activation that lead to the pathophysiological changes of malignant hyperthermia. Objectives: the aim of this study is to perform a literature review on the RyR1 receptor and malignant hyperthermia. The main objective is to describe the mechanism of action of the ryanodine receptor and its implication in the pathology. Methodology: a search was performed in the electronic database pubmed, considering only articles written in English and without restrictions on region and year of publication. The date of the last search was December 20, 2024. Only articles that addressed the pathomechanism of the disease or identified possible new mutations in the receptor were selected. Prior to the search, the following keywords were defined: RyR1, pathomechanism, malignant hyperthermia, mutations and channelopathies. Conclusions: mutations in the RyR1 receptor result in a constant calcium leak at rest, defective excitation-contraction coupling and increased mitochondrial oxidative stress. These mutations alter the kinetics of the channel and render it hypersensitive to channel-activating ligands such as caffeine and halothane.
Introduction: malignant hyperthermia is an autosomal dominant pharmacogenetic disorder affecting skeletal muscle. The associated mutation involves the ryanodine receptor, namely isoform 1 at the level of the sarcoplasmic reticulum. These mutations cause an exaggerated increase in plasma intra calcium concentration, activating biochemical processes related to muscle activation that lead to the pathophysiological changes of malignant hyperthermia. Objectives: the aim of this study is to perform a literature review on the RyR1 receptor and malignant hyperthermia. The main objective is to describe the mechanism of action of the ryanodine receptor and its implication in the pathology. Methodology: a search was performed in the electronic database pubmed, considering only articles written in English and without restrictions on region and year of publication. The date of the last search was December 20, 2024. Only articles that addressed the pathomechanism of the disease or identified possible new mutations in the receptor were selected. Prior to the search, the following keywords were defined: RyR1, pathomechanism, malignant hyperthermia, mutations and channelopathies. Conclusions: mutations in the RyR1 receptor result in a constant calcium leak at rest, defective excitation-contraction coupling and increased mitochondrial oxidative stress. These mutations alter the kinetics of the channel and render it hypersensitive to channel-activating ligands such as caffeine and halothane.
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Keywords
Recetor de Rianodina Patomecanismo Hipertermia Maligna Mutações Ryanodine receptor Pathomechanisms Malignant hyperthermia Mutations