? subunits determine the time course of desensitization in rat ?3 neuronal nicotinic acetylcholine receptors

Cachelin, Armand B.; Jaggi, Rolf

doi:10.1007/bf00370298

Cited by 54 publications

(48 citation statements)

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“…Therefore, the effects of choline on pre-synaptic and somatic/dendritic nAChRs would be expected to be opposite. Also different are the biophysical properties of β2*, β4* and α7 nAChRs (Cachelin and Jaggi, 1991;Fenster et al, 1997;Gerzanich et al, 1994;Bertrand et al, 1992). For instance, the desensitization kinetic of α7 nAChRs is considerably faster than that of β2* and β4* nAChRs (Fenster et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity of nicotinic acetylcholine receptor expression in the caudal nucleus of the solitary tract

Smith

Uteshev

2008

Neuropharmacology

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The nucleus of the solitary tract (NTS) is the principal integrating relay in the processing of visceral sensory and gustatory information. In the present study, patch-clamp electrophysiological experiments were conducted using rat horizontal brainstem sections. Pre-synaptic and somatic/ dendritic nicotinic acetylcholine receptors (nAChRs) expressed in neurons of the caudal NTS (cNTS) were found to be randomly distributed between pre-synaptic and somatic/dendritic sites (χ 2 =0.72, df =3, p>0.87, n=200). Pre-synaptic nAChRs were detected by their facilitating effects on glutamatergic neurotransmission of a sub-population of cNTS neurons (categorized as "effectpositive") upon brief picospritzer applications of 0.1-0.5 mM nicotine. These effects were resistant to inhibition by 20 nM methyllycaconitine (MLA) and 4 μM dihydro-β-erythroidine (DHβE), and were replicated by brief picospritzer applications of 0.2-1 mM cytisine. Picospritzer applications of 0.2 mM RJR-2403, a potent agonist of α4β2 nAChRs, did not facilitate synaptic release of glutamate in effect-positive cNTS neurons. The population of somatic/dendritic nAChRs has been found to be heterogeneous and included nAChRs that were activated by RJR-2403 and/or cytisine; or insensitive to cytisine; or inhibited by MLA. The presented results are consistent with the expression of β4-containing (i.e., β4*) nAChRs, likely α3β4*, in presynaptic terminals of effectpositive cNTS neurons. Somatic/dendritic nAChRs appear to involve both α7 and non-α7 subunits. Heterogeneity in the subunit composition of pre-synaptic and somatic/dendritic nAChRs may underlie diverse roles that these receptors play in regulation of behavioral and visceral reflexes, and may reflect specific targeting by endogenous nicotinic agents and nicotine.

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Section: Discussionmentioning

confidence: 99%

Heterogeneity of nicotinic acetylcholine receptor expression in the caudal nucleus of the solitary tract

Smith

Uteshev

2008

Neuropharmacology

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“…2). Likewise, it is probable that desensitization of the lower affinity putative ␣3␤4*-nAChRs, as observed in various cells representative of both the autonomic nervous system and CNS (Higgins and Berg, 1988;Oortigiesen and Vijverberg, 1989;Mathie et al, 1990;Khiroug et al, 1997Khiroug et al, , 1998Boyd, 1987;Ifune and Steinbach, 1993;Lester and Dani, 1995), in addition to systems designed to specifically express ␣3␤4 receptors (Cachelin and Jaggi, 1991;Hsu et al, 1996;Fenster et al, 1997;Wang et al, 1998;Xiao et al, 1998), can also be explained in terms of the two-state model, although due to the slower time course of desensitization for ␤4 subunit-containing receptors (see below), the biphasic nature may only be seen clearly during longer agonist applications (e.g., Lester and Dani, 1995). Concentration-dependent analyses of desensitization of presumed native ␣3␤4* nAChRs have estimated the affinity of the desensitized state for nicotine to be Ϸ20 -300 nM (Higgins and Berg, 1988;Lester and Dani, 1995).…”

Section: Heteromeric ␣␤* Receptorsmentioning

confidence: 99%

“…Following on from the work of Cachelin and Jaggi (1991), several studies have suggested that the ␤ subunit (␤4/␤2) strongly influences the rate of onset of desensitization: receptors containing ␤2 subunits desensitize faster than those containing ␤4 subunits (Hsu et al, 1995;Fenster et al, 1997;Wang et al, 1998;Bohler et al, 2001). The difference is effectively due to an altered balance of the fast and slow desensitization components: Ͼ90% desensitization for ␤4*nAChRs is slow; Ͼ90% desensitization for ␤2*nAChRs is fast ( Fig.…”

Section: Heteromeric ␣␤* Receptorsmentioning

confidence: 99%

“…The structural basis that governs the dominant role of the ␤ subunit in desensitization kinetics (Cachelin and Jaggi, 1991) has also been recently explored in detail (Bohler et al, 2001). Chimeras between ␤2 and ␤4 subunits showed that the extracellular region from the N-terminal to the beginning of the first transmembrane (TM) domain is sufficient to confer fast and slow kinetics on ␤2 and ␤4 subunit-containing receptors, respectively (Frances et al, 2000;Bohler et al, 2001).…”

Section: Molecular Aspects Of Desensitizationmentioning

confidence: 99%

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Desensitization of neuronal nicotinic receptors

2002

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ABSTRACT:The loss of functional response upon continuous or repeated exposure to agonist, desensitization, is an intriguing phenomenon if not as yet a welldefined physiological mechanism. However, detailed evaluation of the properties of desensitization, especially for the superfamily of ligand-gated ion channels, reveals how the nervous system could make important use of this process that goes far beyond simply curtailing excessive receptor stimulation and the prevention of excitotoxicity. Here we will review the mechanistic basis of desensitization and discuss how the subunit-dependent properties and regulation of nicotinic acetylcholine receptor (nAChR) desensitization contribute to the functional diversity of these channels. These studies provide the essential framework for understanding how the physiological regulation of desensitization could be a major determinant of synaptic efficacy by controlling, in both the short and long term, the number of functional receptors. This type of mechanism can be extended to explain how the continuous occupation of desensitized receptors during chronic nicotine exposure contributes to drug addiction, and highlights the potential significance of prolonged nAChR desensitization that would also occur as a result of extended acetylcholine lifetime during treatment of Alzheimer's disease with cholinesterase inhibitors. Thus, a clearer picture of the importance of nAChR desensitization in both normal information processing and in various diseased states is beginning to emerge.

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“…This may reflect the influence of non-a subunits present within native insect receptors. In a comparable situation in vertebrates, the /3 subunit has, in fact, been shown to be important in determining the time course of desensitisation (Cachelin and Joggi, 1991).…”

Section: Structure -Function Considerations For Insect Nachr Subunitsmentioning

confidence: 99%

Cloning and Functional Characterisation of Two Novel Nicotinic Acetylcholine Receptor α Subunits from the Insect Pest Myzus persicae

Sgard¹,

Fraser

Katkowska

et al. 1998

Journal of Neurochemistry

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Abstract:Nicotinic acetyicholine receptors play a major role in excitatory neurotransmission in insect CNSs and constitute an important target for insecticides. Here, we report the isolation and functional characterisation of two cDNAs encoding nicotinic acetyicholine receptor a subunits from a major insect pest, the peach-potato aphid Myzus persicae. These two subunits, termed Mpal and Mpa2, are respective structural homologues of the Drosophila Da2/Schistocerca gregaria aLl a-subunit pair and the Drosophila ALS a subunit. Xenopus oocyte expression confirmed that each Myzus subunit can form functional acetylcholine-or nicotine-gated channels. However, some electrophysiological and pharmacological properties of the Myzus subunits were distinct from those encoded by the corresponding Drosophila subunits. Coexpression of the Myzus subunits with the chick /32 subunit revealed other differences from the Drosophila system, as only very limited potentiation of agonist-induced currents was observed with Mpa2 and none with Mpal. Available data therefore indicate that structurally homologous insect nicotinic acetylcholine receptor a subunits from different species can exhibit distinctive physiological and pharmacological characteristics.

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? subunits determine the time course of desensitization in rat ?3 neuronal nicotinic acetylcholine receptors

Cited by 54 publications

References 17 publications

Heterogeneity of nicotinic acetylcholine receptor expression in the caudal nucleus of the solitary tract

Heterogeneity of nicotinic acetylcholine receptor expression in the caudal nucleus of the solitary tract

Desensitization of neuronal nicotinic receptors

Cloning and Functional Characterisation of Two Novel Nicotinic Acetylcholine Receptor α Subunits from the Insect Pest Myzus persicae

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