KCNN3

Official Full Name

potassium calcium-activated channel subfamily N member 3

Organism

Homo sapiens

Gene ID

3782

Background

Action potentials in vertebrate neurons are followed by an afterhyperpolarization (AHP) that may persist for several seconds and may have profound consequences for the firing pattern of the neuron. Each component of the AHP is kinetically distinct and is mediated by different calcium-activated potassium channels. This gene belongs to the KCNN family of potassium channels. It encodes an integral membrane protein that forms a voltage-independent calcium-activated channel, which is thought to regulate neuronal excitability by contributing to the slow component of synaptic AHP. This gene contains two CAG repeat regions in the coding sequence. It was thought that expansion of one or both of these repeats could lead to an increased susceptibility to schizophrenia or bipolar disorder, but studies indicate that this is probably not the case. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]

Synonyms

SK3; ZLS3; hSK3; SKCA3; KCa2.3

Cat.No.	Product Name	Price
CSC-RI0110	Human KCNN3 Stable Cell Line-CHO-K1	Inquiry
CSC-DC007997	Panoply™ Human KCNN3 Knockdown Stable Cell Line	Inquiry
CSC-SC007997	Panoply™ Human KCNN3 Over-expressing Stable Cell Line	Inquiry
CSC-RI0110-2	Human KCNN3 Stable Cell Line - HEK293	Inquiry

Cat.No.	Product Name	Price
AD08454Z	Human KCNN3 adenoviral particles	Inquiry
LV16039L	human KCNN3 (NM_002249) lentivirus particles	Inquiry
LV16040L	human KCNN3 (NM_170782) lentivirus particles	Inquiry
LV16041L	human KCNN3 (NM_001204087) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH323611	shRNA set against Human KCNN3 (NM_002249.5)	Inquiry
SHH323615	shRNA set against Mouse KCNN3 (NM_080466.2)	Inquiry
SHL191172	shRNA set against Mouse Kcnn3(NM_080466.2)	Inquiry
SHL191190	shRNA set against Rat Kcnn3(NM_019315.2)	Inquiry

Cat.No.	Product Name	Price
CDFR011406	Rat Kcnn3 cDNA Clone(NM_019315.2)	Inquiry
MiUTR1M-06259	KCNN3 miRNA 3'UTR clone	Inquiry
MiUTR1R-02842	KCNN3 miRNA 3'UTR clone	Inquiry
MiUTR3H-05509	KCNN3 miRNA 3'UTR clone	Inquiry
MiUTR3H-05510	KCNN3 miRNA 3'UTR clone	Inquiry
CDCB189835	Rabbit KCNN3 ORF clone (XM_008264370.1)	Inquiry
CDCL123281	Mouse KCNN3 ORF clone (NM_001204087.1)	Inquiry
CDCL151216	Mouse Kcnn3 ORF clone (NM_080466.2)	Inquiry
CDCR378608	Rat Kcnn3 ORF Clone(NM_019315.2)	Inquiry
CDCS409601	Human KCNN3 ORF Clone (BC042147)	Inquiry

Detailed Information

Recent Research

KCNN3 gene encodes the small conductance Ca²⁺-activated K⁺ (SK) channel 3, also known as SK3 or K_Ca2.3, containing six transmembrane segments. The gene family of SK channels is composed of 4 members (KCNN1-KCNN4) of which the first three are most alike. Four subunits form a functional potassium channel, and calcium sensitivity is achieved by binding to C-terminal calmodulin.

KCNN3 is responsible for I_KCacurrents and is activated by intracellular Ca2+ ions. The up-regulation of KCNN3 contributes to an increase in I_KCa current, modulates cardiac repolarization and it has been reported to have an important role in ventricular tachycardia. Some reports have shown a protective role when the I_KCa current is blockedor a pro-arrhythmic role when the gene is over-expressed. It has a negative effect of this current. Besides, other reports have shown that a blockage of this current promotes the development of ventricular arrhythmias.

KCNN3 is involved in the regulation of vascular tension and blood pressure. Activation of the potassium channel results in hyperpolarization of the endothelial cell which subsequently results inhyperpolarization of the adjacent muscle cell and dilatation of the vessel. One report has shown that conditional repression of the KCNN3 channel results in increased blood pressure in rat mesenteric arteries. Cells lacking KCNN3 showed poor response to the vasodilator acetylcholine and the vascular wall shear stress.

In addition, the SK3 channel has been demonstrated to form heteromultimeric complexes with the KCNN3 in vitro, and blockade of the SK2/3 complex has also been shown to prolong the action potential duration (APD) in isolated cardiomyocytes. In addition, SK3 channel overexpression is associated with sudden death and increases susceptibility to aspectrum in arrhythmia syndrome, including heart block and bradyarrhythmias, AF, and slowed ventricular conduction.Some reports have shown that the protein levels of SK3 were down-regulated by 46% in permanent AF. More importantly, in vivo electrophysiological studies found that the atrial effective refractory periods were significantly shortened in SK3 mutant mice compared with the WT animals, and atrial arrhythmias, mainly AF, were induced in adult SK3 mutant animals.

At last, KCNN3 contributes to the development and progression of numerous solid tumors. In melanoma cells, up-regulation of KCNN3 enhances cell motility by hyperpolarizing the cell membrane potential; in breast cancer cells, KCNN3 is a mediator of cell migration, and together with P2X purinoceptor 7, contributes to cysteine cathepsin-dependent cell invasiveness; and in colon cancer, KCNN3, together with short transient receptor potential channel 1 (TRPC1) and calcium release-activated calcium channel protein 1 (orai-1), regulates store operated calcium entry (SOCE)-dependent cell migration. Furthermore, KCNN3 is up-regulated by a 16-fold change in bortezomib-resistant BN myeloma cells, which suggests that its expression is associated with drug resistance.

References:

Ana O, et al. Patients with Dilated Cardiomyopathy and Sustained Monomorphic Ventricular Tachycardia Show Up-Regulation of KCNN3 and KCNJ2 Genes and CACNG8-Linked Left Ventricular Dysfunction. PLOS ONE, 2015, 10(12):e0145518-.
Mahida S, et al. Overexpression of KCNN3 results in sudden cardiac death. Cardiovascular Research, 2014, 101(2):326-334.
Potier M, et al. The SK3/KCa2.3 potassium channel is a new cellular target for edelfosine. British Journal of Pharmacology, 2015, 162(2):464-479.
Xia L, et al. Low expression of KCNN3 may affect drug resistance in ovarian cancer. Molecular Medicine Reports, 2018.

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