User:ThrowTheBar2/SK Channel Outline

SK Channel Outline

Calcium-activated SK potassium channel
SK Channel
Identifiers
Symbol	SK_channel
Pfam	PF03530
InterPro	IPR011996
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Small Conductance Calcium-activated Potassium (SK) Channel

Classification

 a. Channel protein that is voltage independent
 
 b. Found in the CNS (microglial cells) and PNS

 c. There are subtypes of SK channels;

   i. KCa2 channels (KCa2.1, KCa2.2, and 
   KCa2.3)

   ii. KCa3.1 intermediate conductance channel

Structure

 a. Functional SK/KCa2 channels consist of four sub-units composed of six 
 trans-membrane regions

 b. In mice, and likely humans, SK channels are localized to dendritic spines

Function

 a.SK/KCa2 and IK/KCa2 channels elucidate their multifaceted 
 functions in cell motility, neuronal excitability, neuroprotection, and 
 neuroinflammation 
   i.Regulate the excitability of rat midbrain neurons 
 
 b.Small molecules or toxins seem to reveal critical roles of 
 SK3/KCa2.3 channels in microglial activation
   i.These channels contribute to action potential frequencies

 c. Modulation of channel revealed other possible functions
   i. synaptic plasticity

 d.SK/KCa2 channels act as fine tuning regulators of action potential frequencies, 
 neuronal excitability, and [Ca2+]
   i.SK/KCa2.2-containing channels are responsible for precision of action 
   potential timing

 e.SK/KCa2 channels are emerging candidates to control N-Methyl-D-aspartic 
 acid receptors

Blockers

 a. Apamin or tamapin can inhibit SK channel function in certain microglial cells
   i. Apamin's only mechanism of action is to block SK channels this mechanism does not 
   work on all SK channels however

Modulators

 a. Riluzole, a drug used in patients with amyotrophic lateral sclerosis (ALS) and 
 hereditary cerebellar ataxia, is a potent activator of SK/KCa2 

Role in Parkinson’s Disease

 a. Neuroinflammation is a critical indicator for this disease and SK Channel degradation 
 can increase levels of neuroinflammation
   i.SK/KCa2 channel activity elicits a dual mechanism of action with direct 
   protective effects in neuronal cells and inhibition of inflammatory activities in 
   microglial cells

 b.Modulation of SK/KCa2 channels in dopaminergic neurons regulates neuronal 
 excitability, survival, and neurotransmitter release, making them suitable candidates 
 for therapeutic intervention in pathological conditions related to dopaminergic 
 dysfunction, such as Parkinson’s disease 

References

• Kuiper EF, Nelemans A, Luiten P, Nijholt I, Dolga A, & Eisel U. 2012. K(Ca)2 and k(ca)3 channels in learning and memory processes, and neurodegeneration. Frontiers in Neuropharmacology. 2012;3:107. [doi: 10.3389/fphar.2012.00107]. Epub 2012 June 11.

• Dolga, A.M. & Culmsee, C. 2012. Protective roles for potassium SK/KCa2 channels in microglia and neurons. Frontiers in Neuropharmacology. 2012;3:108. [doi: 10.3389/fphar.2012.00196]. Epub 2012 2012 November 01.

• Faber, E.S.L & Sah, P. 2007 Functions of SK channels in central neurons. Proceedings of the Australian Physiological Society. 2007;34:1077–1083. [PubMed]

• Stocker, M. (2004). Ca2+-activated K+ channels: Molecular determinants and function of the SK family. Nature Reviews. Neuroscience, 5(10), 758-770. [[1]]

• Thu, J.N., Bloodgood, B.L., Lin, M., Sabatini, B.L., Maylie, J. & Adelman, J.P. (2005). SK channels and NMDC receptors from a Ca2+ mediated feedback loop in dendrititc spines. Nature Neuroscience, 8(5), 642-649. [[2]]