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In embryonic neurons, the intracellular chloride concentration is elevated, making GABA and glycine depolarizing. Later in development, coincident with neuronal maturation, the extruding potassium-chloride co-transporter KCC2 is expressed. It reverses the chloride gradient, rendering it hyperpolarizing. Early depolarization is assumed to play trophic roles during nervous system development. I thus decided to investigate the effects of the depolarizing chloride gradient on development in vivo in the zebrafish embryo. I first determined the temporal pattern of KCC2 expression in zebrafish and found it was absent in the embryo. I then over-expressed wild-type, gain-of-function and loss-of-function variants of human KCC2, using GFP-tagged constructs for detection purposes. Over-expression of functional hKCC2 perturbed the morphology and motor behaviours of the embryos. At the cellular level, KCC2 impaired axonal growth and affected the neuronal populations in the brain, hindbrain and spinal cord. This suggests the depolarizing effects of glycine are critical for neurogenesis.

Title page, table of contents and summary only. The complete thesis in print form is available from the University of Adelaide Library. / The results presented in this thesis show the existence of TREK-1(Twik-RElated K+ channel; KCNK2), variant A and C of TREK-2 (KCNK10) and TRAAK (Twik-Related Arachidonic Acid-stimulated K+ channel; KCNK4) in human heart; the localization of TREK-1 and variants of TREK-2 on the membrane and in cytoplasmic areas of human cardiomyocyte; the notably high-level expression of TREK-1 in diseased human heart; the reverse expression of variant A and C of TREK-2 in normal and diseased human heart. These observations strongly indicate TREK channels play important roles in arrhythmia genesis and TREK-sensitive cardiac remodelling within the development of cardiac hypertrophy, ischemia cardiomyopathy and idiopathic dilated cardiomyopathy. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1248412 / Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 2006

Thesis (Ph. D.)--Georgia State University, 2007. / Title from file title page. Chun Jiang, committee chair; Teryl Frey, Deborah Baro, Delon Barfuss, committee members. Electronic text (168 p. : ill. (some col.)) : digital, PDF file. Description based on contents viewed Jan. 30, 2008. Includes bibliographical references (p. 146-151).

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Nevada, Reno, 2008. / "December, 2008." Includes bibliographical references (leaves 227-270). Online version available on the World Wide Web.

Thesis (Ph. D.)--University of Washington, 1998. / Vita. Includes bibliographical references (leaves [126]-169).

Thesis (Ph. D.)--University of Washington, 1998. / Vita. Includes bibliographical references (leaves [114]-152).

Thesis, (Ph. D.)--Oregon Graduate Institute of Science and Technology, 1998.