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The Journal of Neuroscience, November 2, 2005, 25(44):10147-10156; doi:10.1523/JNEUROSCI.3086-05.2005

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Cellular/Molecular
A Drosophila KCNQ Channel Essential for Early Embryonic Development

Hua Wen, * Thomas M. Weiger, * Tanya S. Ferguson, * Mohammad Shahidullah, Samae S. Scott, and Irwin B. Levitan

Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

The mammalian voltage-dependent KCNQ channels are responsible for distinct types of native potassium currents and are associated with several human diseases. We cloned a novel Drosophila KCNQ channel (dKCNQ) based on its sequence homology to the mammalian genes. When expressed in Chinese hamster ovary cells, dKCNQ gives rise to a slowly activating and slowly deactivating current that activates in the subthreshold voltage range. Like the M-current produced by mammalian KCNQ channels, dKCNQ current is sensitive to the KCNQ-specific blocker linopirdine and is suppressed by activation of a muscarinic receptor. dKCNQ is also similar to the mammalian channels in that it binds calmodulin (CaM), and CaM binding is necessary to produce functional currents. In situ hybridization analysis demonstrates that dKCNQ mRNA is present in brain cortical neurons, the cardia (proventriculus), and the nurse cells and oocytes of the ovary. We generated mutant flies with deletions in the genomic sequence of dKCNQ. Embryos produced by homozygous deletion females exhibit disorganized nuclei and fail to hatch, suggesting strongly that a maternal contribution of dKCNQ protein and/or mRNA is essential for early embryonic development.

Key words: KCNQ channels; M-current; Drosophila ion channels; embryonic development; fly mutants; maternal effect

Received Aug 19, 2003; revised September 19, 2005; accepted September 20, 2005.




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