Regulation of slowpoke potassium channel expression in developing and adult neural and muscular systems.

摘要

A precise organization of gene expression is required for developing neural and muscular systems. Steroid hormones are one mechanism to control the expression of genes that are critical for their development. The focus of my research is to determine how the expression of critical regulators of cell excitability, potassium ion channels, are regulated in the hawkmoth, Manduca sexta.;The voltage-gated calcium-activated potassium ion channel, Slowpoke or KCNMA1, is a dynamic integrator of membrane voltage and intracellular calcium. These channels are widely expressed and as a result of their dual activation contribute to cellular excitability and calcium-dependent physiological processes. Chapter 1 demonstrates how the steroid hormone ecdysone regulates slowpoke mRNA levels during adult development to contribute to maturation of the CNS and flight muscle. Near the end of adult development of the Manduca sexta the slowpoke (msslo) transcript levels are abruptly upregulated in the dorsal longitudinal flight muscles (DLMs) and gradually upregulated in the CNS. This msslo upregulation temporally correlates with declining ecdysteroid titers. My results suggest that ecdysteroids regulate msslo expression in the DLMs but not the CNS.;Adult Manduca engage in foraging and mating behaviors that require the flight muscles. Slowpoke currents are the major repolarizing currents in adult flight muscles. Chapter 2 tests the hypotheses that aging affects msslo transcript levels in the DLMs and that muscle activity occurs during flight regulates mRNA levels of these channels throughout the lifespan of the adult. My results indicate that there is an age-dependent decrease in msslo transcript levels and suggest that the expression of msslo is not mediated by muscle activity.;The results detailed in this thesis will improve our understanding of how the spatiotemporal regulation of slowpoke transcription provides a foundation for how these channels contribute to tailoring cell excitability to the differing physiological and behavioral demands during development.