Structure-function studies of Drosophila shaker potassium channels

• Main Author: McCormack, Ken
• Format: Others
• Language: en
• Published: 1991
• Online Access: https://thesis.library.caltech.edu/2922/1/McCormack_k_1991.pdf; McCormack, Ken (1991) Structure-function studies of Drosophila shaker potassium channels. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/63q7-hw24. https://resolver.caltech.edu/CaltechETD:etd-07182007-074159 <https://resolver.caltech.edu/CaltechETD:etd-07182007-074159>

Voltage-dependent ion channels mediate electrical signals in the nervous system; many sodium (Na+), calcium (Ca++) and potassium (K+) selective channels are structurally related, and thus represent a family. These proteins undergo interesting conformational changes in response to alterations in transmembrane potential. However, the functional determinants involved in these transitions are not well understood. Chapters 2A and 2B describe the identification and characterization of an amino acid sequence motif (a leucine-heptad repeat) that is evolutionarily conserved among this family of voltage-dependent ion channels. Conservative, single amino-acid substitutions within this region of Drosophila Shaker (Sh) proteins have substantial effects on the voltage-dependence of activation. The observed alterations suggest that the heptad-repeat region is an important determinant in the conformational transitions leading to channel opening. Na+ and Ca++ channels are composed of four homologous domains, each of which is equivalent to a single K+ channel subunit. Thus, K+ channels are thought to be functional multimers. Furthermore, there are a large number of different voltage-dependent K+ genes and alternatively spliced products that potentially can be expressed in the same cell. Therefore, the potential number of different K+ channel multimers could be quite extensive. Chapter 3 describes the physiological characteristics of combinations of K+ channels belonging to the Sh family that have been coexpressed in Xenopus oocytes. Members of the same molecular class of Sh channel form heteromultimers with novel functional properties, adding to the diversity of K+ channel function. Members of different molecular classes do not form heteromultimeric channels, suggesting that there are distinct K+ channel systems. The Appendix describes an alternative exon in the "constant" region of the Drosophila Sh gene, the existence of which suggests, that the molecular diversity of this gene is greater than previously determined.