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

Vladimir V. Uteshev, Edwin M. Meyer, Roger L. Papke

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72 Scopus citations


Tuberomammillary histamine neurons (TM) of the posterior hypothalamus exclusively express alpha-bungarotoxin (αBgt) sensitive nicotinic receptors, providing a unique model system for studying physiological properties of native α7-like receptors. Here the properties of αBgt-sensitive receptors were investigated using the patch-clamp technique and rapid application of acetylcholine (ACh) or the α7-selective agonists, 3-(4-hydroxy,2-methoxybenzylidene)anabaseine (4OH-GTS-21), and choline. 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 ACh and choline but voltage-independent for 4OH-GTS-21. A slow form of desensitization was present which was relatively agonist-independent and was faster than the rate of 4OH-GTS-21 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 calcium homeostasis over a narrow, but therapeutically important, range of intracellular calcium concentrations. This could then provide the basis for cytoprotective effects of 4OH-GTS-21 and other nicotinic agonists, mediating trophic and neuromodulatory functions.

Original languageEnglish
Pages (from-to)33-46
Number of pages14
JournalBrain Research
Issue number1-2
StatePublished - 6 Sep 2002


  • Acetylcholine
  • Choline
  • Desensitization
  • GTS-21
  • Tuberomammillary nucleus
  • α-Bungarotoxin


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