Small conductance Ca2+-activated potassium channels (SK channels) underlie the after-hyperpolarization that follows an action potential. Within a train of action potentials, progressively longer interspike intervals are due to the medium Al-IP, while the slow AHP underlies spike-frequency adaptation whereby a burst is terminated, regulating burst frequency. A wide range of neurotransmitters increase cAMP levels, inhibiting the slow AHP, suppressing spike-frequency adaptation, and enhancing excitability. Three mammalian SK channels have been cloned, with properties consistent with the medium AHP. However, the relationship of the cloned channels to the slow AHP, and the molecular nature of the channels underlying the slow AHP remain unresolved. The larval muscle preparation from Drosophila provides a model system that has been essential for understanding the molecular physiology of K+ channels. One of the two prominent K+ currents in larval muscle that has not been molecularly identified is a slowly activating, Ca2+-activated K+ conductance, Ics that shares many of the hallmark features of the mammalian slow AHP. The Drosophila genome contains a single SK gene, expressed in embryos, larvae, and adult animals.The driving hypothesis for this application is that the Drosophila ICs is orthologous to the mammalian IsIowAHP. First, we will thoroughly characterize Ics. Second, we will knock out dSK, determine the phenotypic consequences, and test the hypothesis that dSK channels underlie Ics Third, if the dSK gene does not encode the Ics channels, we will clone the gene encoding lcs channels.
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