K channel reorganization and homeostatic plasticity during postembryonic development: biophysical and genetic analyses in acutely dissociated Drosophila central neurons.

Intrinsic electric activities of neurons play important roles in establishing and refining neural circuits during development. However, how the underlying ionic currents undergo postembryonic reorganizations remains largely unknown. Using acutely dissociated neurons from larval, pupal, and adult Drosophila brains, we show drastic re-assemblies and compensatory regulations of voltage-gated (I) and Ca-activated (I) Kcurrents during postembryonic development. Larval and adult neurons displayed prominent fast-inactivating I, mediated by the Shaker (Sh) channel to a large extent, while in the same neurons I was far smaller in amplitude. In contrast, pupal neurons were characterized by large sustained I and prominent I, encoded predominantly by the slowpoke (slo) gene. Surprisingly, deletion of Sh in the Sh null mutant removed inactivating, transient I from large portions of neurons at all stages. Interestingly, elimination of Sh currents was accompanied by upregulation of non-Sh transient I. In comparison, the slo mutation abolished the vast majority of I, particularly at the pupal stage. Strikingly, the deficiency of I in slo pupae was compensated by the transient component of I mediated by Sh channels. Thus, I appears to play critical roles in pupal development and its absence induces functional compensations from a specific transient I current. While mutants lacking either Sh or slo currents survived normally, Sh;;slo double mutants deficient in both failed to survive through pupal metamorphosis. Together, our data highlight significant reorganizations and homeostatic compensations of Kcurrents during postembryonic development and uncover previously unrecognized roles for Sh and slo in this plastic process.