Molecular determinants of BK channel functional diversity and functioning

Ramon Latorre, Karen Castillo, Willy Carrasquel-Ursulaez, Romina V. Sepulveda, Fernando Gonzalez-Nilo, Carlos Gonzalez, Osvaldo Alvarez

Resultado de la investigación: Review article

45 Citas (Scopus)

Resumen

Large-conductance Ca2+- and voltage-activated K+ (BK) channels play many physiological roles ranging from the maintenance of smooth muscle tone to hearing and neurosecretion. BK channels are tetramers in which the pore-forming α subunit is coded by a single gene (Slowpoke, KCNMA1). In this review, we first highlight the physiological importance of this ubiquitous channel, emphasizing the role that BK channels play in different channelopathies. We next discuss the modular nature of BK channel-forming protein, in which the different modules (the voltage sensor and the Ca2+ binding sites) communicate with the pore gates allosterically. In this regard, we review in detail the allosteric models proposed to explain channel activation and how the models are related to channel structure. Considering their extremely large conductance and unique selectivity to K+, we also offer an account of how these two apparently paradoxical characteristics can be understood consistently in unison, and what we have learned about the conduction system and the activation gates using ions, blockers, and toxins. Attention is paid here to the molecular nature of the voltage sensor and the Ca2+ binding sites that are located in a gating ring of known crystal structure and constituted by four COOH termini. Despite the fact that BK channels are coded by a single gene, diversity is obtained by means of alternative splicing and modulatory β and γ subunits. We finish this review by describing how the association of the α subunit with β or with γ subunits can change the BK channel phenotype and pharmacology.

Idioma originalEnglish
Páginas (desde-hasta)39-87
Número de páginas49
PublicaciónPhysiological Reviews
Volumen97
N.º1
DOI
EstadoPublished - 1 ene 2017

Huella dactilar

Large-Conductance Calcium-Activated Potassium Channels
Binding Sites
Neurosecretion
Channelopathies
Alternative Splicing
Hearing
Genes
Smooth Muscle
Maintenance
Pharmacology
Ions
Phenotype

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Physiology (medical)

Citar esto

Latorre, R., Castillo, K., Carrasquel-Ursulaez, W., Sepulveda, R. V., Gonzalez-Nilo, F., Gonzalez, C., & Alvarez, O. (2017). Molecular determinants of BK channel functional diversity and functioning. Physiological Reviews, 97(1), 39-87. https://doi.org/10.1152/physrev.00001.2016
Latorre, Ramon ; Castillo, Karen ; Carrasquel-Ursulaez, Willy ; Sepulveda, Romina V. ; Gonzalez-Nilo, Fernando ; Gonzalez, Carlos ; Alvarez, Osvaldo. / Molecular determinants of BK channel functional diversity and functioning. En: Physiological Reviews. 2017 ; Vol. 97, N.º 1. pp. 39-87.
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Latorre, R, Castillo, K, Carrasquel-Ursulaez, W, Sepulveda, RV, Gonzalez-Nilo, F, Gonzalez, C & Alvarez, O 2017, 'Molecular determinants of BK channel functional diversity and functioning', Physiological Reviews, vol. 97, n.º 1, pp. 39-87. https://doi.org/10.1152/physrev.00001.2016

Molecular determinants of BK channel functional diversity and functioning. / Latorre, Ramon; Castillo, Karen; Carrasquel-Ursulaez, Willy; Sepulveda, Romina V.; Gonzalez-Nilo, Fernando; Gonzalez, Carlos; Alvarez, Osvaldo.

En: Physiological Reviews, Vol. 97, N.º 1, 01.01.2017, p. 39-87.

Resultado de la investigación: Review article

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AU - Castillo, Karen

AU - Carrasquel-Ursulaez, Willy

AU - Sepulveda, Romina V.

AU - Gonzalez-Nilo, Fernando

AU - Gonzalez, Carlos

AU - Alvarez, Osvaldo

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N2 - Large-conductance Ca2+- and voltage-activated K+ (BK) channels play many physiological roles ranging from the maintenance of smooth muscle tone to hearing and neurosecretion. BK channels are tetramers in which the pore-forming α subunit is coded by a single gene (Slowpoke, KCNMA1). In this review, we first highlight the physiological importance of this ubiquitous channel, emphasizing the role that BK channels play in different channelopathies. We next discuss the modular nature of BK channel-forming protein, in which the different modules (the voltage sensor and the Ca2+ binding sites) communicate with the pore gates allosterically. In this regard, we review in detail the allosteric models proposed to explain channel activation and how the models are related to channel structure. Considering their extremely large conductance and unique selectivity to K+, we also offer an account of how these two apparently paradoxical characteristics can be understood consistently in unison, and what we have learned about the conduction system and the activation gates using ions, blockers, and toxins. Attention is paid here to the molecular nature of the voltage sensor and the Ca2+ binding sites that are located in a gating ring of known crystal structure and constituted by four COOH termini. Despite the fact that BK channels are coded by a single gene, diversity is obtained by means of alternative splicing and modulatory β and γ subunits. We finish this review by describing how the association of the α subunit with β or with γ subunits can change the BK channel phenotype and pharmacology.

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Latorre R, Castillo K, Carrasquel-Ursulaez W, Sepulveda RV, Gonzalez-Nilo F, Gonzalez C y otros. Molecular determinants of BK channel functional diversity and functioning. Physiological Reviews. 2017 ene 1;97(1):39-87. https://doi.org/10.1152/physrev.00001.2016