Activation and inhibition of native neuronal alpha-bungarotoxin-sensitive nicotinic XXXX receptors.

@entity1617 @entity1877 @entity55383 @entity460 @entity112 @entity934
Tuberomammillary @entity112 neurons (TM) of the posterior hypothalamus exclusively express alpha-bungarotoxin (alphaBgt) sensitive nicotinic receptors, providing a unique model system for studying physiological properties of native alpha7-like receptors. Here the properties of alphaBgt-sensitive receptors were investigated using the patch-clamp technique and rapid application of @entity934 ( @entity1617 ) or the alpha7-selective agonists, @entity55383 ( @entity55383 ), and @entity1877 . Alpha-Bgt-sensitive receptor responses to rapid application of high agonist concentrations were characterized by a transient current which rapidly decayed in a voltage-independent concentration-dependent manner to a relatively sustained slow current. Upon agonist removal, current persisted for several milliseconds (or longer) and increased above the level of the slow current (rebound). Lower agonist concentrations did not produce a rebound. Our analysis suggests that the current rebound represents a recovery phase from a low potency inhibition. This inhibition was voltage-dependent for @entity1617 and @entity1877 but voltage-independent for @entity55383 . A slow form of desensitization was present which was relatively agonist-independent and was faster than the rate of @entity55383 unbinding. Kinetic analysis revealed that the concentration dependence of the transient response amplitudes was compromised by solution exchange; net charge measurements over the late response phases were chosen as an alternative measure of concentration/response function. Our data suggest that low agonist concentrations can evoke a prolonged or tonic-like receptor activation. Functioning in this modality, receptors would regulate @entity460 homeostasis over a narrow, but therapeutically important, range of intracellular @entity460 concentrations. This could then provide the basis for cytoprotective effects of @entity55383 and other nicotinic agonists, mediating trophic and neuromodulatory functions.
