Cyclic AMP regulates the proportion of functional acetylcholine receptors on chicken ciliary ganglion neurons.

Margiotta, Joseph F.; Berg, Daniela; Dionne, Vincent E.

doi:10.1073/pnas.84.22.8155

Cited by 101 publications

(74 citation statements)

References 38 publications

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“…A potential role for desensitization then, is to act as a shuttle that would allow movement of receptors be- tween functional and nonfunctional pools of receptors [Boyd, 1987; Fig. 2(B)], as implied for the cAMPdependent conversion of silent to functional ganglionic nAChRs during development (Margiotta et al, 1987;see also Fenster et al, 1999b). However, this need not be the case and inactivation and desensitization could be two completely separate processes (Rowell and Duggan, 1998).…”

Section: Regulation Of Desensitizationmentioning

confidence: 99%

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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Section: Regulation Of Desensitizationmentioning

confidence: 99%

Desensitization of neuronal nicotinic receptors

2002

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“…Treatment of CG neurons with VIP increases ACh responses, but not nAChR surface levels, by increasing intracellular cAMP (Gurantz et al, 1994). Elevated cAMP levels enhance ACh responses by converting existing surface nAChRs from a nonfunctional "silent" state to a functional state via posttranslational mechanisms (Margiotta et al, 1987;Vijayaraghavan et al, 1990). Further, CG neurons express the receptors for a second potential input-derived factor, pituitary adenylate cyclase-activating polypeptide (PACAP), a close relative of VIP.…”

Section: Regulatory Signals That Mediate the Effects Of Synaptic Partmentioning

confidence: 99%

Regulatory mechanisms that govern nicotinic synapse formation in neurons

et al. 2002

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Individual cholinoceptive neurons express high levels of different neuronal nicotinic acetylcholine receptor (nAChR) subtypes, and target them to the appropriate synaptic regions for proper function. This review focuses on the intercellular and intracellular processes that regulate nAChR expression in vertebrate peripheral nervous system (PNS) and central nervous system (CNS) neurons. Specifically, we discuss the cellular and molecular mechanisms that govern the induction and maintenance of nAChR expression-innervation, target tissue interactions, soluble factors, and activity. We define the regulatory principles of interneuronal nicotinic synapse differentiation that have emerged from these studies. We also discuss the molecular players that target nAChRs to the surface membrane and the interneuronal synapse.

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“…Although there is no direct support that the change in response amplitude is attributable to the "new" surface nAChRs, it is reassuring to note that disruption of vesicle exocytosis (presumably the supply of the new nAChRs) essentially (Ϸ70%) prevented the functional change. However, it is difficult to eliminate the possibility that (some of) the increased response results from the conversion of nonfunctional to functional preexisting surface ␣7 nAChRs, as proposed for other nAChRs (Margiotta et al, 1987). In addition, it is not possible to dismiss alterations in ␣7 nAChR properties (P o and i).…”

Section: Modes Of ␣7 Nachr Regulation By Tyrosine Phosphorylationmentioning

confidence: 99%

Rapid Upregulation of α7 Nicotinic Acetylcholine Receptors by Tyrosine Dephosphorylation

Cho

Song²,

Leitzell³

et al. 2005

J. Neurosci.

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␣7 nicotinic acetylcholine receptors (nAChRs) modulate network activity in the CNS. Thus, functional regulation of ␣7 nAChRs could influence the flow of information through various brain nuclei. It is hypothesized here that these receptors are amenable to modulation by tyrosine phosphorylation. In both Xenopus oocytes and rat hippocampal interneurons, brief exposure to a broad-spectrum protein tyrosine kinase inhibitor, genistein, specifically and reversibly potentiated ␣7 nAChR-mediated responses, whereas a protein tyrosine phosphatase inhibitor, pervanadate, caused depression. Potentiation was associated with an increased expression of surface ␣7 subunits and was not accompanied by detectable changes in receptor open probability, implying that the increased function results from an increased number of ␣7 nAChRs. Soluble N-ethylmaleimide-sensitive factor attachment protein receptor-mediated exocytosis was shown to be a plausible mechanism for the rapid delivery of additional ␣7 nAChRs to the plasma membrane. Direct phosphorylation/ dephosphorylation of ␣7 subunits was unlikely because mutation of all three cytoplasmic tyrosine residues did not prevent the genisteinmediated facilitation. Overall, these data are consistent with the hypothesis that the number of functional cell surface ␣7 nAChRs is controlled indirectly via processes involving tyrosine phosphorylation.

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Cyclic AMP regulates the proportion of functional acetylcholine receptors on chicken ciliary ganglion neurons.

Cited by 101 publications

References 38 publications

Desensitization of neuronal nicotinic receptors

Desensitization of neuronal nicotinic receptors

Regulatory mechanisms that govern nicotinic synapse formation in neurons

Rapid Upregulation of α7 Nicotinic Acetylcholine Receptors by Tyrosine Dephosphorylation

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