Autoradiographic localization of functional muscarinic receptors in the rat superior cervical sympathetic ganglion reveals an extensive distribution over non-synaptic surfaces of neuronal somata, dendrites and nerve endings

Ramcharan, Eion J.; Matthews, Margaret R.

doi:10.1016/0306-4522(95)00478-5

Cited by 12 publications

(15 citation statements)

References 75 publications

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“…Differential placement is also suggested by efferent stimulation in the frog in that it appears to only activate the fast excitatory response, although, in these same preparations, a slower mAChR-mediated excitation was activated using cholinergic agonists (Bernard et al 1985). Analogous to autonomic ganglia and glutamatergic synapses, cartography of the vestibular efferent synapse may be proposed where nicotinic receptors are typically clustered within the synapse and muscarinic receptors are located perisynaptically (Ramcharan and Matthews 1996;Wakade and Wakade 1983). Differences in localization of muscarinic versus nicotinic receptors may account for the difficulty in activating R DMPP with exogenously applied ACh and failure to activate slow excitatory responses using direct electrical stimulation of efferents.…”

Section: Differential Synaptic Placementmentioning

confidence: 97%

A Pharmacologically Distinct Nicotinic ACh Receptor Is Found in a Subset of Frog Semicircular Canal Hair Cells

Holt

Lioudyno

Guth

2003

Journal of Neurophysiology

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A pharmacologically distinct nicotinic ACh receptor is found in a subset of frog semicircular canal hair cells. J Neurophysiol 90: 1526 -1536, 2003; 10.1152/jn.00273.2002. Frog vestibular organs are endowed with a prominent cholinergic efferent innervation whose stimulation results in several different effects, thereby suggesting diversity in the expression of postsynaptic acetylcholine (ACh) receptors. The application of ACh can mimic efferent stimulation in producing both an inhibition and a facilitation of afferent discharge which are thought to be mediated by at least two distinct ACh receptors present on vestibular hair cells, i.e., ␣9-containing nicotinic receptors (␣9nAChR) and muscarinic receptors (mAChR), respectively. Using patch-clamp and multiunit vestibular afferent recordings, we demonstrate the presence of an additional excitatory hair cell nicotinic ACh receptor pharmacologically distinct from both ␣9nAChR and mAChR. In order of increasing potency, this distinct receptor was activated by ACh, carbachol, and particularly by the selective nicotinic agonist 1,1-dimethyl-4-phenyl-piperazinium (DMPP). This DMPP-sensitive nicotinic receptor (R DMPP ) was antagonized by the classic nicotinic antagonist d-tubocurarine, but refractory to strychnine, atropine, and propylbenzilylcholine mustard, at concentrations that completely block ␣9nAChR and/or mAChR. Activation of R DMPP on application of ACh or DMPP to a subpopulation of isolated posterior semicircular canal (SCC) hair cells resulted in a large depolarization (18.0 Ϯ 1.2 mV). The current underlying this depolarization was typically small (80.1 Ϯ 21.6 pA) and showed an inward rectification starting around Ϫ45 mV. Given their respective EC 50 s (47 nM vs. 20 M), R DMPP was nearly 400 times more sensitive to ACh than ␣9nAChR and thus responded to concentrations of ACh considered too low to be effective at stimulating ␣9nAChR. Despite this remarkable sensitivity, exogenous ACh readily stimulated the mAChR in the intact posterior SCC preparation but failed to activate R DMPP unless the acetylcholinesterase inhibitor physostigmine was present, or high concentrations of ACh were used (Ͼ3 mM). In frog, R DMPP most likely underlies the rapid excitatory response seen during efferent stimulation.

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Section: Differential Synaptic Placementmentioning

confidence: 97%

A Pharmacologically Distinct Nicotinic ACh Receptor Is Found in a Subset of Frog Semicircular Canal Hair Cells

Holt

Lioudyno

Guth

2003

Journal of Neurophysiology

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“…Blockade of M 1 R signaling in satellite cells within the DRG, which then affects neighboring neurons, also cannot be excluded. However, M 1 R expression has not yet been demonstrated in satellite cells, and a study utilizing electron microscopy combined with autoradiography in rat superior cervical ganglia found specific binding of a muscarinic agonist to the M 1 R in neuronal somata and dendrites and not satellite cells (61). Given the possible range of off-target effects of the antimuscarinic drugs, it was promising that, from a therapeutic standpoint, no side effects were observed.…”

Section: +mentioning

confidence: 99%

Selective antagonism of muscarinic receptors is neuroprotective in peripheral neuropathy

Calcutt¹,

Smith²,

Frizzi³

et al. 2017

Journal of Clinical Investigation

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“…Muscarinic receptors on rat sympathetic neurons are widely distributed over their somatic and dendritic surfaces and are not focally concentrated at synapses, as demonstrated in a definitive study by Ramcharan and Matthews (1996) using light and electron microscopic autoradiography.…”

Section: Presynaptic Output In ␣3mentioning

confidence: 84%

“…Muscarinic receptors on rat sympathetic neurons are not focally concentrated at synapses but are widely distributed over their somatic and dendritic surfaces, with higher densities on the soma (Ramcharan and Matthews, 1996). For acetylcholine to reach muscarinic receptors during synaptic transmission, it must diffuse from the synapses (Brown and Selyanko, 1985).…”

Section: Muscarinic Responses On ␣3mentioning

confidence: 99%

A Null Mutation for the α3 Nicotinic Acetylcholine (ACh) Receptor Gene Abolishes Fast Synaptic Activity in Sympathetic Ganglia and Reveals That ACh Output from Developing Preganglionic Terminals Is Regulated in an Activity-Dependent Retrograde Manner

Rassadi¹,

Krishnaswamy²,

Pié³

et al. 2005

J. Neurosci.

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In vertebrates, synaptic activity exerts an important influence on the formation of neural circuits, yet our understanding of its role in directing presynaptic and postsynaptic differentiation during synaptogenesis is incomplete. This study investigates how activity influences synaptic differentiation as synapses mature during early postnatal life. Specifically, we ask what happens to presynaptic terminals when synapses develop without functional postsynaptic receptors and without fast synaptic transmission.To address this issue, we investigated cholinergic nicotinic synapses in sympathetic ganglia of mice with a null mutation for the ␣3 nicotinic ACh receptor gene. Disrupting the ␣3 gene completely eliminates fast excitatory synaptic potentials on postganglionic sympathetic neurons, establishing a crucial role for ␣3-containing postsynaptic receptors in synaptic transmission. Interestingly, the preganglionic nerve terminals form morphologically normal synapses with sympathetic neurons, and these synapses persist without activity in postnatal animals. Surprisingly, when stimulating the preganglionic nerve at physiological rates, we discovered a significant decrease in ACh output from the presynaptic terminals in these ␣3 Ϫ/Ϫ sympathetic ganglia. We show that this decrease in ACh output from the presynaptic terminals results, in part, from a lack of functional high-affinity choline transporters. We conclude the following: (1) fast synaptic transmission in mammalian SCG requires ␣3 expression; (2) in the absence of activity, the preganglionic nerve forms synapses that appear morphologically normal and persist for several weeks; and (3) to sustain transmitter release, developing presynaptic terminals require an activity-dependent retrograde signal.

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Autoradiographic localization of functional muscarinic receptors in the rat superior cervical sympathetic ganglion reveals an extensive distribution over non-synaptic surfaces of neuronal somata, dendrites and nerve endings

Cited by 12 publications

References 75 publications

A Pharmacologically Distinct Nicotinic ACh Receptor Is Found in a Subset of Frog Semicircular Canal Hair Cells

A Pharmacologically Distinct Nicotinic ACh Receptor Is Found in a Subset of Frog Semicircular Canal Hair Cells

Selective antagonism of muscarinic receptors is neuroprotective in peripheral neuropathy

A Null Mutation for the α3 Nicotinic Acetylcholine (ACh) Receptor Gene Abolishes Fast Synaptic Activity in Sympathetic Ganglia and Reveals That ACh Output from Developing Preganglionic Terminals Is Regulated in an Activity-Dependent Retrograde Manner

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