@article{oai:niigata-u.repo.nii.ac.jp:00006477,
 author = {Masaki, Hisashi},
 issue = {1},
 journal = {Acta medica et biologica, Acta medica et biologica},
 month = {Mar},
 note = {The effects of Ca^<2+>, Ba^<2+>, Mg^<2+> and Zn^<2+> on the activity of heteromeric N-methyl-D-aspartate (NMDA) receptor channels (ε1/ζ1, ε2/ζ1, ε3/ζ1 and ε4/ζ1) expressed in Xenopus laevis oocytes were examined using the whole-cell clamp technique. The whole-cell current in response to 10μM glutamate plus 10μM glycine consisted of two phases: an initial spikelike phase and a subsequent sustained phase. Profiles of the sustained phase were almost a plateau in oocytes expressing the ε2/ζ1, ε3/ζ1 and ε4/ζ1 channels and in one third of those expressing the ε1/ζ1 channel. In two thirds of the oocytes expressing the ε1/ζ1 channel, the sustained phase gradually increased. The initial spikelike phase was enhanced as the extracellular Ca^<2+> concentration increased, but the enhancement was suppressed by an intracellular injection of ethyleneglycol-bis(β-aminoethyl ether)-N,N,N'N'-tetraacetic acid (EGTA). Therefore, this spike-like current may be induced by intracellular Ca^<2+>-dependent processes: Ca^<2+>-dependent CI^- -conductance. Extracellular Ca^<2+> suppressed the flat sustained phase in oocytes expressing the ε1/ζ1, ε3/ζ1 and ε4/ζ1 channels in a concentration-dependent manner. However, no comparable effect was observed in oocytes expressing the ε2/ζ1 channel in which the whole-cell current was unchanged at 0.2, 0.6 and 2.0 mM extracellular Ca^<2+>. This sustained phase was unchanged by EGTA injection into oocytes expressing the ε1/ζ1, ε2/ζ1and ε3/ζ1 channels and only partially inhibited in oocytes expressing the ε4/ζ1 channel. Ba^<2+> also inhibited the flat sustained phase in oocytes expressing the ε1/ζ1, ε3/ζ1 and ε4/ζ1 channels, but not those expressing the ε2/ζ1 channel. Mg^<2+> and Zn^<2+> suppressed the sustained current in a concentration-dependent manner in oocytes expressing every heteromeric channel. However, the ε3/ζ1 and ε4/ζ1 channels were more resistant to Mg^<2+> than the ε1/ζ1 and ε2/ζ1 channels. The inhibitory effects of Zn^<2+> on heteromeric NMDA channels were similar to those of Mg^<2+>, except for the ε1/ζ1 channel. The gradually increasing current observed in oocytes expressing the ε1/ζ1 channel was very sensitive to Zn^<2+>, and the sustained phase showed a plateau in the presence of 1μM Zn^<2+>. These diverse sensitivities of heteromeric channels to divalent cations may depend on properties of the ε subunits. The characterization of these heteromeric NMDA channels based on their sensitivities to divalent cations, which is demonstrated in this paper, may be useful in understanding the physiological significance of the molecular diversity of the NMDA receptor channels.},
 pages = {1--10},
 title = {Effects of Divalent Cations on Heteromeric NMDA Receptor Channels Expressed in Xenopus Oocytes},
 volume = {43},
 year = {1995}
}