User:Gloryrunner13/sandbox

1. Summary (Function)
   1. Localized in dendrites and cell body (1)
   2. Mediator of apoptosis in hippocampal, cortical and granule neurons (1)
      1. Apoptosis function induced by increase in reactive oxygen species (ROS)
2. Structure
   1. Functional Alpha Subunit (4), (8)
      1. All K+ channels have a pore of alpha-subunits; one to two copies of a conserved loop P-domain
      2. P-domain contains selectivity sequence allowing only K+ ions, and only those of a certain class (“functional diversity of families”)
      3. Associate with auxiliary cytoplasmic beta subunits
      4. 2 types: 6TM spanning regions, 2TM regions
         1. 6TM: conserved gene families: Kv, KCNQ, EAG-like, and Ca activated
         2. 2TM: inward rectifying
   2. Large number of phosphorylation sites (1)
3. Regulation
   1. Expression is developmentally regulated (1)
   2. Poorly conducting in phosphorylated state (1)
4. Blockers
   1. Selectivity
      1. Stromatoxin- voltage-clamp experiments; low selectivity (2)
      2. Hanatoxin- inhibits K+ voltage gated channel activation (2)
      3. Guangxitoxin-1E- high selectivity for Kv2 channels (2)
5. Kinetics
   1. Repolarization
   2. N- and C-terminal regions are main factors in activation kinetics of this channel. (3) (5)
6. Channelopathies/Mutations
   1. Epileptic Encephalopathy (6)
      1. Developmental Disabilities
         1. Deficiencies in: neurotransmitter regulation, heart rate, insulin production, hearing, etc.
7. Physiological Roles in Diseases
   1. Neurodegenerative Diseases: Oxidative modulation of K2.1 channels contributes to altered excitability, progression of neurodegenerative diseases, and healthy aging. (7)
   2. Diabetes (Pancreatic Bcell Signaling) : K(+) efflux mediated by KV2.1 delayed rectifier K(+) channels acts as a brake for insulin secretion. (9) (10)
   3. Alzheimers: Injury-mediated increased K(+) efflux through Kv2.1 channels promotes neuronal apoptosis, contributing to widespread neuronal loss in neurodegenerative disorders such as Alzheimer's disease. (11)
8. Pharmocology
   1. Anti-apoptotic strategy (1)
      1. CO can protect against an increase in KCNC1 current by regulating ROS and PKG
         1. Cancer cells and chronic viruses produce excess CO

References

1. http://www.wjgnet.com/1949-8454/full/v5/i2/85.htm
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972724/
3. https://www.ncbi.nlm.nih.gov/pubmed/14608450
4. https://www.ncbi.nlm.nih.gov/pubmed/12451110
5. https://www.ncbi.nlm.nih.gov/pubmed/18607586
6. http://www.pcmicroscopycore.com/the-jordyn-project-kcbn1
7. https://www.ncbi.nlm.nih.gov/pubmed/25333910
8. https://www.ebi.ac.uk/interpro/entry/IPR005400
9. https://www.ncbi.nlm.nih.gov/pubmed/25052376
10. https://www.ncbi.nlm.nih.gov/pubmed/20711225
11. https://www.ncbi.nlm.nih.gov/pubmed/24323720