Depression of a sustained calcium current by kainate in rat hippocampal neurones in vitro.

1. High-threshold, slow inactivating inward Ca2+ currents were studied in CA1 pyramidal neurones from rat hippocampal slices using the single-electrode voltage clamp technique. 2. Kainate (50-400 nM) induced a dose-dependent depression of the amplitude of the slow Ca2+ current. At a dose of 200 nM the current amplitude was reduced from -0.63 +/- -0.06 to -0.32 +/- 0.06 nA. Such an effect of kainate was associated with the development of a small inward current (-0.11 +/- 0.03 nA). Kynurenic acid (1 mM) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 microM) fully prevented these actions of kainate. 3. The structurally related kainate analogue alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA; 200 nM) depressed the slow Ca2+ current by 30 +/- 7%, an effect also blocked by CNQX. 4. In low-Na+ medium slow Ca2+ currents were followed by sustained inward tail currents. Kainate reduced both the steady-state Ca2+ current (from -0.98 +/- 0.14 to -0.63 +/- 0.15 nA) and the tail current (from -0.40 +/- 0.04 to -0.14 +/- 0.03 nA). 5. The inactivation process of the slow Ca2+ current was tested by a double-pulse protocol and was found to be enhanced by kainate. 6. Equimolar replacement of Ca2+ by Ba2+ produced larger inward currents followed by prolonged tails. Kainate reduced the Ba2+ steady-state current from -1.77 +/- 0.18 to -1.44 +/- 0.24 nA and the tail current from -0.47 +/- 0.15 to -0.17 +/- 0.05 nA. 7. In current clamp experiments Ca2+ action potentials were recorded from cells loaded with the Ca2+ chelator BAPTA. In these conditions kainate failed to reduce the Ca2+ action potential, while in the absence of BAPTA kainate shortened the Ca2+ action potentials by 30%. 8. It is suggested that low concentrations of kainate reduced the slow Ca2+ current by promoting its inactivation perhaps through a rise in free intracellular Ca2+.