Changes in cationic selectivity of the nicotinic channel at the rat ganglionic synapse: a role for chloride ions?

The permeability of the nicotinic channel (nAChR) at the ganglionic synapse has been examined, in the intact rat superior cervical ganglion in vitro, by fitting the Goldman current equation to the synaptic current (EPSC) I-V relationship. Subsynaptic nAChRs, activated by neurally-released acetylchol...

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Main Authors: Oscar Sacchi, Maria Lisa Rossi, Rita Canella, Riccardo Fesce
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3045433?pdf=render
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spelling doaj-0aa82bea33a6446289acf1cbe0616c752020-11-25T02:39:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0162e1731810.1371/journal.pone.0017318Changes in cationic selectivity of the nicotinic channel at the rat ganglionic synapse: a role for chloride ions?Oscar SacchiMaria Lisa RossiRita CanellaRiccardo FesceThe permeability of the nicotinic channel (nAChR) at the ganglionic synapse has been examined, in the intact rat superior cervical ganglion in vitro, by fitting the Goldman current equation to the synaptic current (EPSC) I-V relationship. Subsynaptic nAChRs, activated by neurally-released acetylcholine (ACh), were thus analyzed in an intact environment as natively expressed by the mature sympathetic neuron. Postsynaptic neuron hyperpolarization (from -40 to -90 mV) resulted in a change of the synaptic potassium/sodium permeability ratio (P(K)/P(Na)) from 1.40 to 0.92, corresponding to a reversible shift of the apparent acetylcholine equilibrium potential, E(ACh), by about +10 mV. The effect was accompanied by a decrease of the peak synaptic conductance (g(syn)) and of the EPSC decay time constant. Reduction of [Cl(-)](o) to 18 mM resulted in a change of P(K)/P(Na) from 1.57 (control) to 2.26, associated with a reversible shift of E(ACh) by about -10 mV. Application of 200 nM αBgTx evoked P(K)/P(Na) and g(syn) modifications similar to those observed in reduced [Cl(-)](o). The two treatments were overlapping and complementary, as if the same site/mechanism were involved. The difference current before and after chloride reduction or toxin application exhibited a strongly positive equilibrium potential, which could not be explained by the block of a calcium component of the EPSC. Observations under current-clamp conditions suggest that the driving force modification of the EPSC due to P(K)/P(Na) changes represent an additional powerful integrative mechanism of neuron behavior. A possible role for chloride ions is suggested: the nAChR selectivity was actually reduced by increased chloride gradient (membrane hyperpolarization), while it was increased, moving towards a channel preferentially permeable for potassium, when the chloride gradient was reduced.http://europepmc.org/articles/PMC3045433?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Oscar Sacchi
Maria Lisa Rossi
Rita Canella
Riccardo Fesce
spellingShingle Oscar Sacchi
Maria Lisa Rossi
Rita Canella
Riccardo Fesce
Changes in cationic selectivity of the nicotinic channel at the rat ganglionic synapse: a role for chloride ions?
PLoS ONE
author_facet Oscar Sacchi
Maria Lisa Rossi
Rita Canella
Riccardo Fesce
author_sort Oscar Sacchi
title Changes in cationic selectivity of the nicotinic channel at the rat ganglionic synapse: a role for chloride ions?
title_short Changes in cationic selectivity of the nicotinic channel at the rat ganglionic synapse: a role for chloride ions?
title_full Changes in cationic selectivity of the nicotinic channel at the rat ganglionic synapse: a role for chloride ions?
title_fullStr Changes in cationic selectivity of the nicotinic channel at the rat ganglionic synapse: a role for chloride ions?
title_full_unstemmed Changes in cationic selectivity of the nicotinic channel at the rat ganglionic synapse: a role for chloride ions?
title_sort changes in cationic selectivity of the nicotinic channel at the rat ganglionic synapse: a role for chloride ions?
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2011-01-01
description The permeability of the nicotinic channel (nAChR) at the ganglionic synapse has been examined, in the intact rat superior cervical ganglion in vitro, by fitting the Goldman current equation to the synaptic current (EPSC) I-V relationship. Subsynaptic nAChRs, activated by neurally-released acetylcholine (ACh), were thus analyzed in an intact environment as natively expressed by the mature sympathetic neuron. Postsynaptic neuron hyperpolarization (from -40 to -90 mV) resulted in a change of the synaptic potassium/sodium permeability ratio (P(K)/P(Na)) from 1.40 to 0.92, corresponding to a reversible shift of the apparent acetylcholine equilibrium potential, E(ACh), by about +10 mV. The effect was accompanied by a decrease of the peak synaptic conductance (g(syn)) and of the EPSC decay time constant. Reduction of [Cl(-)](o) to 18 mM resulted in a change of P(K)/P(Na) from 1.57 (control) to 2.26, associated with a reversible shift of E(ACh) by about -10 mV. Application of 200 nM αBgTx evoked P(K)/P(Na) and g(syn) modifications similar to those observed in reduced [Cl(-)](o). The two treatments were overlapping and complementary, as if the same site/mechanism were involved. The difference current before and after chloride reduction or toxin application exhibited a strongly positive equilibrium potential, which could not be explained by the block of a calcium component of the EPSC. Observations under current-clamp conditions suggest that the driving force modification of the EPSC due to P(K)/P(Na) changes represent an additional powerful integrative mechanism of neuron behavior. A possible role for chloride ions is suggested: the nAChR selectivity was actually reduced by increased chloride gradient (membrane hyperpolarization), while it was increased, moving towards a channel preferentially permeable for potassium, when the chloride gradient was reduced.
url http://europepmc.org/articles/PMC3045433?pdf=render
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