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The voltage-sensitive cardiac M2 muscarinic receptor modulates the inward rectification of the G protein-coupled, ACh-gated K+ current.
Salazar-Fajardo, Pedro D; Aréchiga-Figueroa, Iván A; López-Serrano, Ana Laura; Rodriguez-Elias, Julio C; Alamilla, Javier; Sánchez-Chapula, José A; Tristani-Firouzi, Martin; Navarro-Polanco, Ricardo A; Moreno-Galindo, Eloy G.
Afiliação
  • Salazar-Fajardo PD; Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de Julio 965, Colonia Villa San Sebastián, C.P, 28045, Colima, COL, Mexico.
  • Aréchiga-Figueroa IA; CONACyT, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, SLP, Mexico.
  • López-Serrano AL; Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de Julio 965, Colonia Villa San Sebastián, C.P, 28045, Colima, COL, Mexico.
  • Rodriguez-Elias JC; Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de Julio 965, Colonia Villa San Sebastián, C.P, 28045, Colima, COL, Mexico.
  • Alamilla J; CONACyT, Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, COL, Mexico.
  • Sánchez-Chapula JA; Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de Julio 965, Colonia Villa San Sebastián, C.P, 28045, Colima, COL, Mexico.
  • Tristani-Firouzi M; Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, 84112, USA. Martin.Tristani@utah.edu.
  • Navarro-Polanco RA; Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de Julio 965, Colonia Villa San Sebastián, C.P, 28045, Colima, COL, Mexico. magdal@ucol.mx.
  • Moreno-Galindo EG; Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de Julio 965, Colonia Villa San Sebastián, C.P, 28045, Colima, COL, Mexico. eloy@ucol.mx.
Pflugers Arch ; 470(12): 1765-1776, 2018 12.
Article em En | MEDLINE | ID: mdl-30155776
The acetylcholine (ACh)-gated inwardly rectifying K+ current (IKACh) plays a vital role in cardiac excitability by regulating heart rate variability and vulnerability to atrial arrhythmias. These crucial physiological contributions are determined principally by the inwardly rectifying nature of IKACh. Here, we investigated the relative contribution of two distinct mechanisms of IKACh inward rectification measured in atrial myocytes: a rapid component due to KACh channel block by intracellular Mg2+ and polyamines; and a time- and concentration-dependent mechanism. The time- and ACh concentration-dependent inward rectification component was eliminated when IKACh was activated by GTPγS, a compound that bypasses the muscarinic-2 receptor (M2R) and directly stimulates trimeric G proteins to open KACh channels. Moreover, the time-dependent component of IKACh inward rectification was also eliminated at ACh concentrations that saturate the receptor. These observations indicate that the time- and concentration-dependent rectification mechanism is an intrinsic property of the receptor, M2R; consistent with our previous work demonstrating that voltage-dependent conformational changes in the M2R alter the receptor affinity for ACh. Our analysis of the initial and time-dependent components of IKACh indicate that rapid Mg2+-polyamine block accounts for 60-70% of inward rectification, with M2R voltage sensitivity contributing 30-40% at sub-saturating ACh concentrations. Thus, while both inward rectification mechanisms are extrinsic to the KACh channel, to our knowledge, this is the first description of extrinsic inward rectification of ionic current attributable to an intrinsic voltage-sensitive property of a G protein-coupled receptor.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Potenciais de Ação / Miócitos Cardíacos / Receptor Muscarínico M2 / Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G Tipo de estudo: Diagnostic_studies Limite: Animals Idioma: En Revista: Pflugers Arch Ano de publicação: 2018 Tipo de documento: Article País de afiliação: México País de publicação: Alemanha
Texto completo
Adicionar na Minha BVS
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XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Potenciais de Ação / Miócitos Cardíacos / Receptor Muscarínico M2 / Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G Tipo de estudo: Diagnostic_studies Limite: Animals Idioma: En Revista: Pflugers Arch Ano de publicação: 2018 Tipo de documento: Article País de afiliação: México País de publicação: Alemanha