Voltage and concentration dependence of Ca(2+) permeability in recombinant glutamate receptor subtypes.
The channels associated with glutamate receptor (GluR) subtypes, namely N-methyl-D-aspartate receptors (NMDARs), and Ca(2+)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) and kainate receptors (KARs), are to varying degrees permeable to Ca(2+). To compare the mechanism of Ca(2+) influx, we measured Ca(2+) permeability relative to that of Na(+) (P(Ca)/P(Na)) using fractional Ca(2+) currents (P(f)) and reversal potential measurements over a wide voltage and Ca(2+) concentration range in recombinant NMDAR NR1-NR2A, AMPAR GluR-A(Q) and KAR GluR-6(Q) channels. For NR1-NR2A channels, P(Ca)/P(Na) derived from P(f) measurements was voltage independent but showed a weak concentration dependence. A stronger concentration dependence was found when P(Ca)/P(Na) was derived from changes in reversal potentials on going from a Na(+) reference solution to a solution with Ca(2+) as the only permeant ion ('biionic' condition). In contrast, P(Ca)/P(Na) was concentration independent when derived from changes in reversal potentials on going from a Na(+) reference solution to the same solution with added Ca(2+) ('high monovalent' condition). For GluR-A(Q) channels, P(Ca)/P(Na) derived from all three approaches was concentration independent, and for the reversal potential-based approaches were of comparable magnitude. Their most distinctive property was that P(Ca)/P(Na) derived from P(f) measurements was strongly voltage dependent. For GluR-6(Q) channels, P(Ca)/P(Na) derived from P(f) measurements was weakly voltage dependent. On the other hand, P(Ca)/P(Na) derived from all three approaches was the most strongly concentration dependent of any GluR subtype and, except for low Ca(2+) concentrations, the values were of comparable magnitude. Thus, the three Ca(2+)-permeable GluR subtypes showed unique patterns of Ca(2+) permeability, indicating that distinct biophysical and molecular events underlie Ca(2+) influx in each subtype.
Jatzke
Claudia
C
Department of Neurobiology and Behavior, State University of New York at Stony Brook, Stony Brook, NY 11794-5230, USA.
Watanabe
Junryo
J
Wollmuth
Lonnie P
LP
D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism*; D002413:Cations, Divalent / Q000378:metabolism; D002460:Cell Line; D004594:Electrophysiology; D006801:Humans; D008954:Models, Biological; D009994:Osmolar Concentration; D010539:Permeability; D018091:Receptors, AMPA / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D002118:Calcium; D002413:Cations, Divalent; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D012964:Sodium