Synaptic plasticity and locomotor behavior are altered by mutations in a novel ion channel. H.A. Nash ¹, R.L. Scott ¹, R. Allada ², K.F. Osborne ¹, D.J. Sandstrom ¹. 1) Laboratory of Molecular Biology, National Institute of Mental Health, NIH, Bethesda, MD 20892; 2) Department of Neurobiology and Physiology, Northwestern University, Evanston IL 60208.

   The Drosophila genome contains 6 genes for ion channels of the four-repeat superfamily. Two are voltage-gated sodium channels and three are voltage-gated calcium channels. The sixth, a1U, encodes an unusual member that, although more closely related to the calcium than the sodium channels, has several distinctive features in its pore and S4 motifs that preclude a definitive in silico assignment of function. We have found a set of mutations, identified by their effects on halothane anesthesia, that lie in this gene. As judged by Western blots, the mutations severely disrupt synthesis and/or stability of the channel protein in adult heads. Immunohistochemistry shows that the wild-type protein is widely distributed in neuropilar regions of the brain, with most intense staining in a broad band of the outer medulla and in a row of cells in the lamina. The a1U ion channel appears to be involved in circadian control of locomotor activity. When tested in a 12/12 cycle, the mutants fail to anticipate the LD transitions. And although they transiently increase activity after lights-off they fail to do so after lights-on, a pattern seen with mutations in the cyc and Clock genes. A clue to the nature of the channel comes from studies of the larval neuromuscular junction (NMJ). When bathed in low calcium buffer, mutant NMJs show enhanced synaptic facilitation to 1 Hz trains of stimuli. This suggests that the a1U channel influences neural function by regulating calcium flux in neurons.