Evolutionary and functional study of K channels--in search for the origin of Shaker channels and a functional study of an Elk channel

Open Access
Author:
Liu, Hansi
Graduate Program:
Biology
Degree:
Master of Science
Document Type:
Master Thesis
Date of Defense:
None
Committee Members:
  • Timothy J Jegla, Thesis Advisor
Keywords:
  • Potassium Channel
  • Shaker
  • Elk
  • Cnidarian
  • Ctenophore
Abstract:
Voltage-gated potassium channels are important for maintaining normal excitability of nervous system. In this study, I investigated the origin of Shaker family channels in basal metazoans and the function of a mammalian Elk channel. Phylogenetic analysis indicates that Shaker-related genes are present in Ctenophores. We identified two Ctenophore M.leidyi Shaker subfamily genes with a silent/regulatory phenotype: these genes encode subunits that only form functional channels when co-expressed with other metazoan Shaker subfamily subunits. We also traced the diversification of Shaker subfamily channels back to Cnidaria through functional analysis of Nematostella Shab, Shaw and Shal currents. The second part of this thesis describes the generation of a Kv12.2 gain-of-function mouse model. We replaced the native mouse Kv12.2 allele with a modified Kv12.2 gene that gives rise to gain-of-function phenotype when heterologously expressed in Xenopus oocyte. In this primary study, these mice exhibited normal responses to varies types of induced seizures.