Small conductance Ca2+-activated potassium channels (SK channels) underlie the after-hyperpolarization that follows an action potential. Within a train of action potentials, progressively longer interspike intervals are due to the medium Al-IP, while the slow AHP underlies spike-frequency adaptation whereby a burst is terminated, regulating burst frequency. A wide range of neurotransmitters increase cAMP levels, inhibiting the slow AHP, suppressing spike-frequency adaptation, and enhancing excitability. Three mammalian SK channels have been cloned, with properties consistent with the medium AHP. However, the relationship of the cloned channels to the slow AHP, and the molecular nature of the channels underlying the slow AHP remain unresolved. The larval muscle preparation from Drosophila provides a model system that has been essential for understanding the molecular physiology of K+ channels. One of the two prominent K+ currents in larval muscle that has not been molecularly identified is a slowly activating, Ca2+-activated K+ conductance, Ics that shares many of the hallmark features of the mammalian slow AHP. The Drosophila genome contains a single SK gene, expressed in embryos, larvae, and adult animals.The driving hypothesis for this application is that the Drosophila ICs is orthologous to the mammalian IsIowAHP. First, we will thoroughly characterize Ics. Second, we will knock out dSK, determine the phenotypic consequences, and test the hypothesis that dSK channels underlie Ics Third, if the dSK gene does not encode the Ics channels, we will clone the gene encoding lcs channels.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM058259-05
Application #
6542982
Study Section
Molecular, Cellular and Developmental Neurosciences 2 (MDCN)
Program Officer
Shapiro, Bert I
Project Start
1998-08-03
Project End
2006-07-31
Budget Start
2002-08-01
Budget End
2003-07-31
Support Year
5
Fiscal Year
2002
Total Cost
$347,755
Indirect Cost
Name
Oregon Health and Science University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
Morgan, L W; Feldman, J F; Bell-Pedersen, D (2001) Genetic interactions between clock mutations in Neurospora crassa: can they help us to understand complexity? Philos Trans R Soc Lond B Biol Sci 356:1717-24
Litt, M; LaMorticella, D; Bond, C T et al. (1999) Gene structure and chromosome mapping of the human small-conductance calcium-activated potassium channel SK1 gene (KCNN1). Cytogenet Cell Genet 86:70-3