KCNS3 Membrane Protein Introduction

Introduction of KCNS3

KCNS3, potassium voltage-gated channel subfamily S member 3 is a protein that in humans is encoded by the KCNS3 gene. It is also called Kv9.3. The protein encoded by this gene is a voltage-gated potassium channel subunit. This potassium channel subunit does not form functional channels by itself, but it can form functional heterotetrameric channels with KCNB1 to modulate the delayed rectifier voltage-gated potassium channel activation and deactivation rates of KCNB1.

Function of KCNS3 Membrane Protein

KCNS3 belongs to the S subfamily of the potassium channel family. It does not form functional channels by itself, but can form functional heterotetrameric channels with KCNB1, and modulate the delayed rectifier voltage-gated potassium channel activation and deactivation rates of KCNB1. The heterotetrameric channel activity shows increased current amplitude with the threshold for action potential activation shifted towards more negative values in hypoxic-treated pulmonary artery smooth muscle cells. Its main functions are associated with the regulation of the resting membrane potential and the control of the shape and frequency of action potentials. KCNS3 are associated with FEV1 in Health ABC participants. Moreover, KCNS3 can be treated as a potential marker for PV neurons, and it might be used to characterize the cell-type specific molecular alterations of cortical GABA neurotransmission. Also, KCNS3 plays a functional role in developing the new treatments to target PV and/or SST neurons in schizophrenia.

Fig.1 Functional Implications of Reduced Kv2.1/Kv9.3 Channel Expression in Cortical Parvalbumin Neurons in Schizophreniaa (Georgiev, 2014)

Application of KCNS3 Membrane Protein in Literature

1. Georgiev D., et al. Cortical Gene Expression After a Conditional Knockout of 67 kDa Glutamic Acid Decarboxylase in Parvalbumin Neurons. Schizophr Bull. 2016, 42(4):992-1002. PubMed ID: 26980143
   
   

   This article suggests that downregulation of GAD67 expression in PV neurons is not related to the lower levels of GABA-associated transcripts, or the characteristic behaviors, in schizophrenia.

2. Sandberg C.J., et al. Transcriptional profiling of adult neural stem-like cells from the human brain. PLoS One. 2014, 9(12):e114739. PubMed ID: 25514637
   
   

   This article identifies KCNS3 is heterogeneously expressed in spheres. This indicates that KCNS3 receptors can serve as new markers for the identification and characterization of neural stem- and progenitor cells or as targets for manipulation of cellular fate.

3. Reardon B.J., et al. Vitamin D-responsive SGPP2 variants associated with lung cell expression and lung function. BMC Med Genet. 2013, 14:122. PubMed ID: 24274704
   
   

   This study shows that the candidate genes including KCNS3 are associated with FEV1 in Health ABC participants.

4. Georgiev D., et al. Lower gene expression for KCNS3 potassium channel subunit in parvalbumin-containing neurons in the prefrontal cortex in schizophrenia. Am J Psychiatry. 2014, 171(1):62-71. PubMed ID: 24170294
   
   

   This article reveals that in prefrontal cortical parvalbumin neurons KCNS3’s expression is suppressed in schizophrenia, providing new insight into the process.

5. Georgiev D., et al. Selective expression of KCNS3 potassium channel α-subunit in parvalbumin-containing GABA neurons in the human prefrontal cortex. PLoS One. 2012, 7(8):e43904. PubMed ID: 22937123
   
   

   This article indicates that KCNS3 can be used as a selective marker of PV neurons, and it might be useful to characterize the cell-type specific molecular alterations of cortical GABA neurotransmission and to develop the new treatments targeting PV and/or SST neurons in schizophrenia.

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Reference

1. Georgiev D, et al. (2014). Lower gene expression for KCNS3 potassium channel subunit in parvalbumin-containing neurons in the prefrontal cortex in schizophrenia. Am J Psychiatry. Jan;171(1):62-71.

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