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Molecular cloning, functional properties, and distribution of rat brain alpha 7: a nicotinic cation channel highly permeable to calcium

P Seguela, J Wadiche, K Dineley-Miller, JA Dani and JW Patrick
Journal of Neuroscience 1 February 1993, 13 (2) 596-604; DOI: https://doi.org/10.1523/JNEUROSCI.13-02-00596.1993
P Seguela
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030.
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J Wadiche
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030.
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K Dineley-Miller
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030.
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JA Dani
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030.
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JW Patrick
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030.
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Abstract

A full-length clone coding for the rat alpha 7 nicotinic receptor subunit was isolated from an adult brain cDNA library and expressed in Xenopus oocytes. A significant proportion of the current through alpha 7-channels is carried by Ca2+. This Ca2+ influx then activates a Ca(2+)- dependent Cl- conductance, which is blocked by the chloride channel blockers niflumic and fluflenamic acid. Increasing the external NaCl concentration caused the reversal potentials for the alpha 7-channels and the Ca(2+)-dependent Cl- channels to be shifted in opposite directions. Under these conditions, agonist application activates a biphasic current with an initial inward current through alpha 7- channels followed by a niflumic acid- and fluflenamic acid-blockable outward current through Ca(2+)-dependent Cl- channels. A relative measure of the Ca2+ permeability was made by measuring the shift in the reversal potential caused by adding 10 mM Ca2+ to the external solution. Measurements made in the absence of Cl-, to avoid artifactual current through Ca(2+)-activated Cl- channels, indicate that alpha 7- homooligomeric channels have a greater relative Ca2+ permeability than the other nicotinic ACh receptors. Furthermore, alpha 7-channels have an even greater relative Ca2+ permeability than the NMDA subtype of glutamate receptors. High levels of alpha 7-transcripts were localized by in situ hybridization in the olfactory areas, the hippocampus, the hypothalamus, the amygdala, and the cerebral cortex. These results imply that alpha 7-containing receptors may play a role in activating calcium-dependent mechanisms in specific neuronal populations of the adult rat limbic system.

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The Journal of Neuroscience: 13 (2)
Journal of Neuroscience
Vol. 13, Issue 2
1 Feb 1993
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Molecular cloning, functional properties, and distribution of rat brain alpha 7: a nicotinic cation channel highly permeable to calcium
P Seguela, J Wadiche, K Dineley-Miller, JA Dani, JW Patrick
Journal of Neuroscience 1 February 1993, 13 (2) 596-604; DOI: 10.1523/JNEUROSCI.13-02-00596.1993

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Molecular cloning, functional properties, and distribution of rat brain alpha 7: a nicotinic cation channel highly permeable to calcium
P Seguela, J Wadiche, K Dineley-Miller, JA Dani, JW Patrick
Journal of Neuroscience 1 February 1993, 13 (2) 596-604; DOI: 10.1523/JNEUROSCI.13-02-00596.1993
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