Molecular cloning, functional properties, and distribution of rat brain alpha 7: a nicotinic cation channel highly permeable to calcium.
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.
Séguéla
P
P
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030.
Wadiche
J
J
Dineley-Miller
K
K
Dani
J A
JA
Patrick
J W
JW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001923:Brain Chemistry; D002038:Bungarotoxins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002412:Cations; D018118:Chloride Channels; D003001:Cloning, Molecular; D004553:Electric Conductivity; D005260:Female; D005439:Flufenamic Acid / Q000494:pharmacology; D007473:Ion Channels / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology; D008969:Molecular Sequence Data; D009544:Niflumic Acid / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism; D010539:Permeability; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D012965:Sodium Chloride / Q000494:pharmacology; D014018:Tissue Distribution; D014162:Transfection; D014982:Xenopus laevis
D002038:Bungarotoxins; D002412:Cations; D018118:Chloride Channels; D007473:Ion Channels; D008565:Membrane Proteins; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D012965:Sodium Chloride; D009544:Niflumic Acid; D005439:Flufenamic Acid; D002118:Calcium