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The Journal of Neuroscience, January 1, 1998, 18(1):16-25

Regulation of Ca²⁺-Dependent K⁺ Channel Expression in Rat Cerebellum during Postnatal Development

Yunhua Li Muller¹, Raven Reitstetter¹, and Andrea J. Yool^{1, 2}

¹ Department of Physiology and ² Department of Pharmacology and the Program in Neuroscience, University of Arizona College of Medicine, Tucson, Arizona 85724-5051

Potassium channels govern duration and frequency of excitable membrane events and may regulate signals that are important in neuronal development. This study assesses the developmental expression of the large conductance Ca²⁺-dependent K⁺ channel in vivo and in vitro in rat cerebellum. In vivo, transcript levels for the Ca²⁺-dependent K⁺ channel (K_Ca) were shown by Northern analysis to increase during development, whereas transcript levels for the voltage-gated K⁺ channel Kv3.1, a delayed rectifier (K_D), remained relatively constant. A comparable pattern was demonstrated by expression in Xenopus oocytes of poly(A)-enriched RNA isolated from postnatal rat cerebella. In cerebellar cultures, increased external K⁺ provided a simple manipulation of cell excitability that influenced K_Ca transcript levels during development. With low external K⁺ (5.3 mM), the levels of K_Ca channel transcript (assessed by semiquantitative PCR) remained constant throughout development. However, in culture medium that supported significant dendritic outgrowth (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 stimuli increased K_Ca expression. The stimulatory effects of increased K⁺ or TEA on K_Ca expression required extracellular Ca²⁺ and were abolished in low external calcium (0.1 mM, buffered with EGTA), although morphological development and survival were not impaired. The regulation of K_Ca channel expression by depolarization and Ca²⁺ entry provides evidence of a logical feedback mechanism governing Ca²⁺ signals that may be significant in cerebellar development.

Key words: calcium-dependent K⁺ channel; rat cerebellum; transcription; mslo; rslo; BK channel; calbindin; depolarization; quantitative PCR

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18116-10$05.00/0

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