DEVELOPMENTAL ALTERATION IN GABA(A) RECEPTOR STRUCTURE AND PHYSIOLOGICAL-PROPERTIES IN CULTURED CEREBELLAR GRANULE NEURONS

Although we now have extensive knowledge about the GABA(A) receptor su bunits determining benzodiazepine modulation of channel function, litt le is known about subunits influencing other modulatory sites on the G ABA(A) receptor-chloride channel complex. We have identified a develop mental change in subunit composition of the GABA(A) receptor in cultur ed cerebellar granule neurons that eliminates benzodiazepine-mediated enhancement of GABA responses and alters modulation by a substituted g amma-butyrolactone. Based on data from sequential PCR experiments, we mimicked the functional properties of early and mature receptors with heterologous expression of specific subunit combinations. This report describes one of the most extensive cell- and site-specific developmen tal changes for an ion channel seen to date.