Permeation of calcium through excitatory amino acid receptor channels in cultured rat hippocampal neurones.

1. N‐methyl‐D‐aspartate (NMDA)‐, quisqualate‐ and kainate‐induced currents were recorded in cultured rat hippocampal neurones using the whole‐cell voltage‐clamp technique. To isolate the inward currents carried by Ca2+ and other divalent cations (Sr2+, Ba2+, Mn2+ and Mg2+), both Na+ and K+ in the control external solution were replaced with the impermeant cation N‐methylglucamine (NMG). 2. Replacement of Na+, K+ and Ca2+ with NMG abolished NMDA‐, quisqualate‐ and kinate‐induced inward currents. In Na(+)‐, K(+)‐free (abbreviated simply as Na(+)‐free) solution containing 10 mM‐Ca2+ NMDA caused prominent inward currents at ‐60 mV. In this solution with the internal solution containing 165 mM‐Cs+, the reversal potential of the NMDA‐induced current was ‐5.0 +/‐ 0.7 mV (n = 36), indicating a value of PCa/PCs = 6.2 for the ratio of the permeability coefficients of Ca2+ and Cs+ according to the constant‐field equation. 3. NMDA elicited inward current responses at ‐60 mV in Na(+)‐, Ca2(+)‐free solution containing 10 mM‐Sr2+, Ba2+, or Mn2+, but not in Na(+)‐free, 10 mM‐Mg2+ solution. On the basis of reversal potential measurements, the permeability sequence of NMDA receptor channels among the divalent cations was determined to be Ba2+ (1.2) greater than Ca2+ (1.0) greater than Sr2+ (0.8) greater than Mn2+ (0.3) much greater than Mg2+ (less than 0.02). 4. The reversal potential of the quisqualate‐induced current was more negative than ‐80 mV in Na(+)‐free, 10 mM‐Ca2+ solution, indicating a value of PCa/PCs less than 0.18. 5. Kainate‐induced current responses were classified into two types. In the type I response the reversal potential of the kainate‐induced current was more negative than ‐80 mV in Na(+)‐free, 10 mM‐Ca2+ solution, indicating that the Ca2+ permeability of this type of kainate channel is as low as that of the quisqualate channel. In the neurones which showed a type I response, there was a tendency of outward rectification in the current‐voltage plots of the kainate response in control solution. 6. In the type II response kainate caused prominent inward currents at ‐60 mV in Na(+)‐free, 10 mM‐Ca2+ solution. The reversal potential was ‐23.3 +/‐ 5.6 mV (n = 17), indicating a permeability ratio PCa/PCs = 2.3. In the neurones which showed a type II response, a remarkable inward rectification was observed in the current‐voltage plots of the kainate response in control solution. 7. Type II kainate channels showed relatively poor selectivity among divalent cations.(ABSTRACT TRUNCATED AT 400 WORDS)