Small conductance calcium-activated potassium channels (SK channels) serve a fundamental role in excitable cells. Activated by elevated levels of intracellular calcium, SK channels mediate the slow after hyperpolarization, the sAHP, which follows the action potential spike. During a sustained stimulus, a train of action potentials is elicited and the depth and extent of the sAHP are increased with each action potential such that the cell is ultimately unable to fire a subsequent action potential even though the stimulus to fire remains. This phenomenon is termed 'spike-frequency adaptation' and protects the cell from tetanic stimulation and associated cell toxicity. Subtypes of SK channels may be distinguished by different sensitivities to the bee venom peptide toxin apamin. Application of apamin to regions of the brain alters physiologically important processes, such as sleep patterns and learning and memory. While the sAHP in most neurons is apamin-sensitive, in some neurons such as hippocampal pyramidal cells, the sAHP is apamin-insensitive, shows a slower time course, and is modulated by activation of protein kinase A (PKA).

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM058259-01
Application #
2693285
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1998-08-03
Project End
2002-07-31
Budget Start
1998-08-03
Budget End
1999-07-31
Support Year
1
Fiscal Year
1998
Total Cost
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