INIBIBB   05455
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BAHIA BLANCA
Unidad Ejecutora - UE
artículos
Título:
Stoichiometry for activation of neuronal a7 nicotinic receptors.
Autor/es:
NATALIA ANDERSEN; JEREMÍAS CORRADI; STEVEN M SINE; CECILIA BOUZAT
Revista:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Editorial:
NATL ACAD SCIENCES
Referencias:
Lugar: Washington DC, USA; Año: 2013 vol. 110 p. 20819 - 20824
ISSN:
0027-8424
Resumen:
Neuronal á7 nicotinic receptors elicit rapid cation influx in response
to acetylcholine (ACh) or its hydrolysis product choline.
They contribute to cognition, synaptic plasticity, and neuroprotection
and have been implicated in neurodegenerative and neuropsychiatric
disorders. á7, however, often localizes distal to sites of
nerve-released Ach and binds ACh with low affinity, and thus
elicits its biological response with low agonist occupancy. To assess
the function of á7 when ACh occupies fewer than five of its
identical binding sites, we measured the open-channel lifetime of
individual receptors in which four of the five ACh binding sites
were disabled. To improve the time resolution of the inherently
brief á7 channel openings, background mutations or a potentiator
was used to increase open duration. We find that, in receptors
with only one intact binding site, the open-channel lifetime is
indistinguishable from receptors with five intact binding sites,
counter to expectations from prototypical neurotransmitter-gated
ion channels where the open-channel lifetime increases with the
number of binding sites occupied by agonist. Replacing the membrane-
embedded domain of á7 by that of the related 5-HT3A receptor
increases the number of sites that need to be occupied to
Q:8 achieve the maximal open-channel lifetime, thus revealing a unique
interdependence between the detector and actuator domains of
these receptors. The distinctive ability of a single occupancy to elicit
a full biological response adapts á7 to volume transmission, a prevalent
mechanism of ACh-mediated signaling in the nervous system
Q:9 and nonneuronal cells.