Magnesium potentiation of the function of native and recombinant GABA(A) receptors.
Mg2+ decreased basal and GABA-inhibited t-butylbicyclophosphoro[35S]thionate binding to GABAA receptor ion channels in rat brain sections up to 1 mM, but increased the binding at 10 mM. The Mg2+-effect was detectable in the presence of a specific GABA site competitive antagonist. Two-electrode voltage clamp recordings of recombinant alpha1beta2gamma2S, alpha1beta2, alpha2beta2gamma2S and alpha2beta2 GABAA receptors revealed a potentiation by 0.1-1 mM Mg2+ of EC20 GABA-evoked ion currents. At 10 mM, Mg2+ decreased the currents. In the absence of GABA, Mg2+ did not evoke any currents. The results show that physiologically relevant Mg2+ concentrations affect the GABA responses on GABAA receptors in native and the main recombinant receptor subtypes, suggesting putative Mg2+ binding sites on the receptor complex.
Möykkynen
T
T
Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland.
Uusi-Oukari
M
M
Heikkilä
J
J
Lovinger
D M
DM
Lüddens
H
H
Korpi
E R
ER
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D003292:Convulsants / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004594:Electrophysiology; D015636:Magnesium Chloride / Q000494:pharmacology*; D008297:Male; D009865:Oocytes / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D003292:Convulsants; D011963:Receptors, GABA-A; D011994:Recombinant Proteins; D015636:Magnesium Chloride; D005680:gamma-Aminobutyric Acid; C037476:tert-butylbicyclophosphorothionate