Dr. Zakon proposes to use the communication signal of a weakly electric fish as a model system to elucidate how ion currents are regulated and the significance of this regulation for behavior. The electric organ discharge (EOD) is sexually-dimorphic, hormone-sensitive, and individually-distinct; the waveshape of the EOD is intimately dependent on and reflective of the membrane properties of cells in the output motor system. The investigators wish to understand how the magnitudes and kinetics of the ion currents in the emitter--the electrocytes--shape the signal, and how they are regulated. In particular, they wish to characterize the delayed rectifying K+ current further, understand what processes give rise to the systematic variation in its kinetics, and how these may be regulated by sex steroids. They will test whether variation in current kinetics is influenced by phosphorylation and/or transcriptional control of the channel (i.e. different channel genes, splicing or editing within a single channel gene, or the expression of a beta subunit). In addition they will study how the magnitude of both the K+ and Na+ currents are co-regulated by second messengers and how this results in changes in the amplitude of the signal around the fish; these changes in signal amplitude likely influence the distance over which these signals are received in the fish's environment. Understanding how ion channels function and are regulated is critical to our fundamental knowledge of excitable cells, especially as malfunctions of ion channels are increasingly recognized in a variety of diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS025513-10
Application #
6051061
Study Section
Special Emphasis Panel (ZRG1-IFCN-6 (01))
Program Officer
Kitt, Cheryl A
Project Start
1989-08-01
Project End
2003-11-30
Budget Start
2000-01-01
Budget End
2000-12-31
Support Year
10
Fiscal Year
2000
Total Cost
$312,264
Indirect Cost
Name
University of Texas Austin
Department
Zoology
Type
Schools of Arts and Sciences
DUNS #
City
Austin
State
TX
Country
United States
Zip Code
78712
Zakon, Harold H (2012) Adaptive evolution of voltage-gated sodium channels: the first 800 million years. Proc Natl Acad Sci U S A 109 Suppl 1:10619-25
Markham, Michael R; McAnelly, M Lynne; Stoddard, Philip K et al. (2009) Circadian and social cues regulate ion channel trafficking. PLoS Biol 7:e1000203
Liu, He; Wu, Ming-ming; Zakon, Harold H (2008) A novel Na+ channel splice form contributes to the regulation of an androgen-dependent social signal. J Neurosci 28:9173-82
McAnelly, M Lynne; Zakon, Harold H (2007) Androgen modulates the kinetics of the delayed rectifying K+ current in the electric organ of a weakly electric fish. Dev Neurobiol 67:1589-97
Liu, He; Wu, Ming-Ming; Zakon, Harold H (2007) Individual variation and hormonal modulation of a sodium channel beta subunit in the electric organ correlate with variation in a social signal. Dev Neurobiol 67:1289-304
Few, W Preston; Zakon, Harold H (2007) Sex differences in and hormonal regulation of Kv1 potassium channel gene expression in the electric organ: molecular control of a social signal. Dev Neurobiol 67:535-49
Stoddard, Philip K; Zakon, Harold H; Markham, Michael R et al. (2006) Regulation and modulation of electric waveforms in gymnotiform electric fish. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 192:613-24
Zakon, Harold H; Lu, Ying; Zwickl, Derrick J et al. (2006) Sodium channel genes and the evolution of diversity in communication signals of electric fishes: convergent molecular evolution. Proc Natl Acad Sci U S A 103:3675-80
Novak, Alicia E; Jost, Manda C; Lu, Ying et al. (2006) Gene duplications and evolution of vertebrate voltage-gated sodium channels. J Mol Evol 63:208-21
Bass, Andrew H; Zakon, Harold H (2005) Sonic and electric fish: at the crossroads of neuroethology and behavioral neuroendocrinology. Horm Behav 48:360-72

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