INVESTIGADORES
BOUZAT Cecilia Beatriz
artículos
Título:
The interface between extracellular and transmembrane domains of homomeric Cys-loop receptors governs channel lifetime and rate of desensitization
Autor/es:
BOUZAT C; BARTOS M; CORRADI J; SINE S
Revista:
JOURNAL OF NEUROSCIENCE
Editorial:
Society for Neuroscience
Referencias:
Año: 2008 vol. 28 p. 7808 - 7819
ISSN:
0270-6474
Resumen:
The lifetimes of activated postsynaptic receptor channels contribute to the efficiency of synaptic transmission. Here we show that
structural differences within the interface dividing extracellular and transmembrane domains of homomeric 7 and 5-HT3A receptors
account for the large differences in open-channel lifetime and time of desensitization onset between these contrasting members of the
Cys-loop receptor superfamily. For7 receptors, agonist-evoked single-channel currents appear mainly as isolated brief openings (o
0.35 ms), whereas macroscopic currents after a step pulse of agonist desensitize rapidly (d0.4 ms). In contrast for 5-HT3A receptors,
agonist-evoked single-channel currents appear as clusters of many long openings in quick succession (cluster1.2 s), whereas macroscopic
currents desensitize slowly (d1.1 s). A chimeric7-5HT3A receptor exhibits functional properties intermediate between those
of the parent receptors, but the functional signatures of each parent are reconstituted after substituting the major loops within the
interface of the extracellular and transmembrane domains from the corresponding parent receptor. Furthermore, these structural loops
contribute to open-channel lifetime and time of desensitization onset in a nonadditive manner. The results suggest that desensitization
is the major determinant of the lifetimes of activated7 and 5-HT3A receptors and that functional differences between the two receptors
arise primarily through structural differences at the interface between extracellular and transmembrane domains.