REGULATION OF CA2-DEPENDENT K+ CHANNEL EXPRESSION IN RAT CEREBELLUM DURING POSTNATAL-DEVELOPMENT()

Potassium channels govern duration and frequency of excitable membrane events and may regulate signals that are important in neuronal develo pment. This study assesses the developmental expression of the large c onductance Ca2+-dependent K+ channel in vivo and in vitro in rat cereb ellum. In vivo, transcript levels for the Ca2+-dependent KC channel (K -Ca) were shown by Northern analysis to increase during development, w hereas transcript levels for the voltage-gated K+ channel Kv3.1, a del ayed rectifier (K-D), remained relatively constant. A comparable patte rn was demonstrated by expression in Xenopus oocytes of poly(A)-enrich ed RNA isolated from postnatal rat cerebella. In cerebellar cultures, increased external K+ provided a simple manipulation of cell excitabil ity that influenced K-Ca transcript levels during development. With lo w external K+ (5.3 mM), the levels of K-Ca channel transcript (assesse d by semiquantitative PCR) remained constant throughout development. H owever, in culture medium that supported significant dendritic outgrow th (10 mM extracellular K+), an upregulation of K-Ca transcript level was observed similar to that seen in vivo. Tetraethylammonium (TEA; 1 mM) similarly enhanced K-Ca expression, suggesting that depolarizing s timuli increased K-Ca expression. The stimulatory effects of increased K+ or TEA on K-Ca expression required extracellular Ca2+ and were abo lished in low external calcium (0.1 mM, buffered with EGTA), although morphological development and survival were not impaired. The regulati on of K-Ca channel expression by depolarization and Ca2+ entry provide s evidence of a logical feedback mechanism governing Ca2+ signals that may be significant in cerebellar development.