potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3 Synonyms: SK3 hSK3 SKCA3 KCa2.3 KCNN3. Symbol: Kcnn3
Small conductance Ca2+ -activated K+ channels (SK chan-
nels) are important regulators of excitability, endogenous
firing pattern and synaptic integration in many neurons
(Bond et al., 2005 ).
Pyramidal neurons of the cortex and hippocampus display a
calcium-activated slow afterhyperpolarization (sAHP) that plays
a key role in regulating cell firing (Schwindt et al., 1988a ,b ;
Stocker et al., 1999 ) and is the target for regulation by multiple
neurotransmitters (Nicoll, 1988 ). Biophysical and electrophysiological studies have suggested that this sAHP is mediated by a
calcium-activated potassium current. However, despite extensive
studies, the identity of the ion channels underlying the sAHP
remains uncertain (Sah and Faber, 2002 ; Vogalis et al., 2003 [13).
In the mid-1990s, with the discovery of the SKCa family of
potassium channels (KCa2.x) (Kohler et al., 1996 ; Gutman et al.,
2003 ), the search for the ion channels responsible for the sAHP
appeared to have reached fruition (Vergara et al., 1998 ; Bond et
al., 1999 ). But the slow AHP current in a transgeneic mouse, expressing a truncated SKCa subunit (SK3-1B)
capable of acting as a dominant negative for the entire family of SKCa–IKCa channels contradicted those findings: Expression of SK3-1B profoundly inhibited medium AHP current
but again had no discernable effect on IsAHP. These results are inconsistent with the proposal that SKCa channels mediate IsAHP in
pyramidal cells and indicate that a different potassium channel mediates this current. (Villalobos )
Kcnn3 : potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3
The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
integral to membrane
Penetrating at least one phospholipid bilayer of a membrane. May also refer to the state of being buried in the bilayer with no exposure outside the bilayer. When used to describe a protein, indicates that all or part of the peptide sequence is embedded in the membrane.
Native SK channels have a characteristic pharmacology. They can be blocked by the bee venom toxin apamin
and several selective small molecule blockers that we have developed (such as UCL 1848) that are active at nanomolar or
subnanomolar concentrations (Chen , Faber ).
SK3 forms functional heteromeric channels with SK1 and SK2. (Monaghan )
CyPPA was found to be a positive modulator of hSK3. (Hougaard )
SK channels and the peripherally
expressed intermediate conductance Ca2+ -activated K+
channel (IK; Ishii et al., 1997), constitute a molecular family
of voltage-independent channels, that are gated by Ca2+
binding to calmodulin (CAM) tightly associated with a CAM-
binding domain (CAMBD) in the C-terminal region (Xia
et al., 1998 ; Khanna et al., 1999 ). Crystallographic data from
C-terminal peptides of the SK2 channel indicate that dimers of CAMBD associate with two CAM molecules, each binding
1 or 2 Ca2+ at the EF hand motifs 1 and 2 (Schumacher et al.,
SK3 channel expression is punctate in nature and largely confined to varicose fibers, which likely represent subcellular compartments of high synaptic. Only occasionally, somatic immunostaining was observed like in the locus coeruleus or in tegmental nuclei. 
Central nervous system
SK3 is primarily expressed in subcortical regions , substantia nigra, amygdala, caudate nucleus, thalamus, hippocampus, ventral tegmental area, cerebellum, corpus callosum and spinal cord , .
For further information about the expression of SK in CNS and their function see Pedarzani and Stocker 2008. 
SK3 shows distinctive distribution to the small intestine, rectum, omentum, myometrium, skeletal muscles, lymphocytes, prostate, heart, kidney, pituitary gland, liver, pancreas and colon.
Rat, mouse and cat spinal cord show a differential and overlapping expression of SK2 and SK3 isoforms across specific types of α-motoneurons. In rodents, SK2 is expressed in all α-motoneurons whereas SK3 is expressed preferentially in small-diameter ones; in cats, SK3 is expressed in all α-motoneurons. 
SK3 channels in muscle cells are crucial for
pregnancy progresses such as myometrial tranquility. SK3 channels are the first
channels for which overexpression led to a delay or cessation
of parturition (Pierce , Bond ).