Changes in the number, function, and regulation of nicotinic acetylcholine receptors during neuronal development

Margiotta, Joseph F.; Gurantz, Devorah

doi:10.1016/0012-1606(89)90183-8

Cited by 83 publications

(95 citation statements)

References 46 publications

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“…The α5 subunit is necessary for the formation of high-conductance channels, but α5 requires the presence of another α-type subunit to form functional nAChR complexes 26,27 . Moreover, the timing of the shift from low-to high-conductance channels in developing CG neurons 28 suggests that the α5 subunit is a relatively late comarticles Fig. 2.…”

Section: Discussionmentioning

confidence: 99%

“…Exogenous myc-tagged protein and endogenous nAChR levels on CG neurons from RCASBP-infected embryos were assayed. Ganglia were acutely dissociated in a calcium-free avian basal salt solution using collagenase (4.0 mg/ml; Type IV; Boehringer Mannheim) for 45 min at 37°C and plated onto silane (Aldrich) coated 24-well culture dishes at one or two CG equivalents per well as described 28 . Cells were incubated in blocking solution (3% BSA and 10% normal horse serum in PBS, pH 7.4), followed by either 10 nM mouse anti-myc mAb 9E10 or 10 nM rat anti-nAChR mAb 35 in avian basal salt solution containing 10% horse serum, and washed, all for 10 min each.…”

Section: Retroviral Vector-mediated Gene Transfer To Ciliary Ganglionmentioning

confidence: 99%

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The long internal loop of the α3 subunit targets nAChRs to subdomains within individual synapses on neurons in vivo

et al. 1998

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ResultsUsing PCR, we constructed chimeric subunits in which the α7 cytoplasmic loop immediately after TM3 and before TM4 was replaced with the homologous region of the α3 or α5 sequence (Fig. 1a). The N-terminus up to TM2 regulates intersubunit assembly into receptor complexes, and α7 subunits do not coassemble with nAChR subunits, as demonstrated for endogenous subunits in CG neurons and for chimeric α7 subunits expressed in Xenopus laevis oocytes 4,5,12,13 . In particular, we have observed that coexpression of chimeric α7 subunits containing the α3 cytoplasmic loop together with wild-type α3 and β4 subunits in Xenopus oocytes results in the formation of two distinct receptor types that have the pharmacological properties of Bgt-nAChRs and nAChRs, respectively (data not shown). Thus, a difference in the distribution of chimeric α7 as compared to wild-type α7 on the infected CG neuron surface would result from the added α3 or α5 cytoplasmic loop. It cannot be explained by assembly with an endogenous nAChR subunit that can target to the synapse. Different types of neurotransmitter receptors coexist within single neurons and must be targeted to discrete synaptic regions for proper function. In chick ciliary ganglion neurons, nicotinic acetylcholine receptors (nAChRs) containing α3 and α5 subunits are concentrated in the postsynaptic membrane, whereas α-bungarotoxin receptors composed of α7 subunits are localized perisynaptically and excluded from the synapse. Using retroviral vector-mediated gene transfer in vivo, we show that the long cytoplasmic loop of α3 targets chimeric α7 subunits to the synapse and reduces endogenous nAChR surface levels, whereas the α5 loop does neither. These results show that a particular domain of one subunit targets specific receptor subtypes to the interneuronal synapse in vivo. Moreover, our findings suggest a difference in the mechanisms that govern assembly of interneuronal synapses as compared to the neuromuscular junction in vertebrates.1998 Nature America Inc.• http://neurosci.nature.com 1998 Nature America Inc.• http://neurosci.nature.com

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Section: Discussionmentioning

confidence: 99%

Section: Retroviral Vector-mediated Gene Transfer To Ciliary Ganglionmentioning

confidence: 99%

The long internal loop of the α3 subunit targets nAChRs to subdomains within individual synapses on neurons in vivo

et al. 1998

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“…Chick ciliary ganglion neurons were dissociated from embryos of White Leghorn chicks as previously described (Margiotta & Gurantz, 1989). Briefly, the ganglia were taken from embryos, killed by rapid decapitation, cut in half, incubated with 1 mg ml-' collagenase (Type A, Boehringer Mannheim) for 30 min at 37°C, and transferred to culture medium consisting of Eagle's minimal essential medium (GIBCO) supplemented with 3% (v/v) chick embryo eye extract (Nishi & Berg, 1981).…”

Section: Methods Preparationmentioning

confidence: 99%

Patch‐clamp analysis of glycine‐induced currents in chick ciliary ganglion neurons.

Zhang

Berg

1995

The Journal of Physiology

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1. The whole-cell configuration of the patch-clamp technique was used to analyse currents induced by glycine in chick ciliary ganglion neurons freshly dissociated from 14-to 15-dayold embryos. 2. Application of glycine to cells voltage-clamped at -60 mV induced inward currents in all neurons tested. Dose-response curves yielded an EQ50 of about 50 /M. Similar responses were elicited by fl-alanine and taurine though higher concentrations were required. 3. Strychnine reversibly inhibited the glycine-induced responses. The effect was dose dependent with a half-maximal effect being obtained with 20 nm strychnine.4. Glycine-induced currents were inhibited by 100 /UM Zn2+. The inhibition had slow rates of onset and recovery, in contrast to Zn2+ inhibition of GABA responses. Both bicuculline and d-tubocurarine inhibited glycine responses in a dose-dependent manner. 5. The steady-state I-V curve for glycine-induced currents was linear over the range -60 to +60 mV, but showed an outward rectification at very hyperpolarized membrane potentials. The reversal potential of glycine-induced currents shifted with changes in intracellular chloride concentration in a manner expected for chloride-selective channels. 6. Expression of functional glycine receptors during development was examined at embryonic day 8 (E8), 11, 14, and 18. The mean peak current was about 60-fold larger at E14 than at E8 and vastly exceeded changes in cell size. During the same period, responses to GABA increased only 2-fold in amplitude and correlated with changes in cell size. 7. The results indicate that autonomic neurons have chloride-selective glycine receptors similar to those found in the CNS and that the receptors are developmentally regulated.

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“…nAChR subunit transcript and protein levels increase significantly during the period of pre-and postganglionic synapse formation (Jacob, 1991;Corriveau and Berg, 1993;Devay et al, 1994;Mandelzys et al, 1994;Levey et al, 1995). Functional nAChRs at the neuronal cell surface also change during this period, with developmental increases in ACh current density and maturational changes in the relative abundance and kinetics of nAChR conductance classes (Margiotta and Gurantz, 1989;Moss et al, 1989;Engisch and Fischbach, 1990;Moss and Role, 1993). These changes in nAChR expression are likely to increase the efficacy of synaptic transmission.…”

Section: Normal Developmental Expression Of Nachrsmentioning

confidence: 99%

“…A notable developmental difference is that ␣5 expression in CG neurons becomes dependent on retrograde target-derived signals after postganglionic synapse formation. This is an interesting change because ␣5 subunits may be necessary for the formation of high conductance nAChR channels and mature functional properties (Margiotta and Gurantz, 1989;Ramirez-Latorre et al, 1996;Wang et al, 1996;Sivilotti et al 1997;Yu and Role, 1998). Axotomy also decreases perisynaptic ␣7-nAChR total protein levels by fourfold, but with a more rapid time course relative to that of ␣3-nAChRs (Jacob and Berg, 1987).…”

Section: Maintenance Of Nachrs Also Requires Target Tissue Interactionsmentioning

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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Changes in the number, function, and regulation of nicotinic acetylcholine receptors during neuronal development

Cited by 83 publications

References 46 publications

The long internal loop of the α3 subunit targets nAChRs to subdomains within individual synapses on neurons in vivo

The long internal loop of the α3 subunit targets nAChRs to subdomains within individual synapses on neurons in vivo

Patch‐clamp analysis of glycine‐induced currents in chick ciliary ganglion neurons.

Regulatory mechanisms that govern nicotinic synapse formation in neurons

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