The interaction of ryanoids with individual ryanodine receptor channels
Biol. Res
; 37(4): 527-538, 2004. tab, graf
Artigo
em Inglês
| LILACS
| ID: lil-437506
Biblioteca responsável:
CL1.1
ABSTRACT
Ryanodine binds with high affinity and specificity to a class of Ca2+-release channels known as ryanodine receptors (RyR). The interaction with RyR results in a dramatic alteration in function with open probability (Po) increasing markedly and rates of ion translocation modified. We have investigated the features of ryanodine that govern the interaction of the ligand with RyR and the mechanisms underlying the subsequent alterations in function by monitoring the effects of congeners and derivatives of ryanodine (ryanoids) on individual RyR2 channels. While the interaction of all tested ryanoids results in an increased Po, the amplitude of the modified conductance state depends upon the structure of the ryanoid. We propose that different rates of cation translocation observed in the various RyR-ryanoid complexes represent different conformations of the channel stabilized by specific conformers of the ligand. On the time scale of a single channel experiment ryanodine binds irreversibly to the channel. However, alterations in structure yield some ryanoids with dissociation rate constants orders of magnitude greater than ryanodine. The probability of occurrence of the RyR-ryanoid complex is sensitive to trans-membrane voltage, with the vast majority of the influence of potential arising from a voltage-driven alteration in the affinity of the ryanoid-binding site.
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Base de dados:
LILACS
Assunto principal:
Rianodina
/
Retículo Sarcoplasmático
/
Canal de Liberação de Cálcio do Receptor de Rianodina
Limite:
Animais
Idioma:
Inglês
Revista:
Biol. Res
Assunto da revista:
Biologia
Ano de publicação:
2004
Tipo de documento:
Artigo
País de afiliação:
Reino Unido
Instituição/País de afiliação:
Imperial College London/GB