Heterogeneous current responses to GABA and glycine are present in post-natally cultured hippocampal neurons

In a patch-clamp study of cultured hippocampal neurons, heterogeneous desensitization responses were observed in all cells with GABAA-gated channels, but in only 5% of cells with glycine-gated channels. GABA- and glycine-activated whole-cell currents from 'fast' and 'slow' cells had very similar amplitudes of about 2.0 nA, but different time-courses of desensitization. Single-channel main conductance states obtained from slow and fast cells both had values of about 27 +/- 1 pS for GABA, and values of 24 +/- 1.8 pS for slow and 19 +/- 1.5 pS for fast desensitizing glycine-gated channels. For GABA, the channel open or burst frequency of fast desensitizing cells was about twice that of slow desensitizing ones, whereas for glycine, the opening frequency of slow desensitizing cells was double that of fast desensitizing cells. Pronounced outward rectification was observed for all but the fast desensitizing glycine-gated cells. Dose-response curves obtained for slow and fast desensitizing cells displayed similar degrees of cooperativity and antagonist affinity, but clearly greater GABA sensitivity for fast desensitizing cells. In contrast, fast desensitizing glycine-gated cells displayed low antagonist affinity, whereas both types of cells displayed similar agonist sensitivity and cooperativity. These results indicate a mosaic-like distribution of different GABAA and glycine receptor isoforms in hippocampal neurons, with the possible existence of pre-natal-like glycine receptor subunits at this early stage of post-natal life.