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KCa5.1

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Target not currently curated in GtoImmuPdb

Target id: 387

Nomenclature: KCa5.1

Family: Calcium- and sodium-activated potassium channels (KCa, KNa)

Contents:

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 0 1149 8p11.23 KCNU1 potassium calcium-activated channel subfamily U member 1 6
Mouse 7 0 1121 8 A2 Kcnu1 potassium channel, subfamily U, member 1 5
Rat 6 1 1113 16q12.4 Kcnu1 potassium calcium-activated channel subfamily U member 1 2
Previous and Unofficial Names Click here for help
Kcnma3 | KCNMC1 | Slo3 | potassium channel
Database Links Click here for help
Alphafold A8MYU2 (Hs), O54982 (Mm)
Ensembl Gene ENSG00000215262 (Hs), ENSMUSG00000031576 (Mm), ENSRNOG00000014741 (Rn)
Entrez Gene 157855 (Hs), 16532 (Mm), 680912 (Rn)
Human Protein Atlas ENSG00000215262 (Hs)
KEGG Gene hsa:157855 (Hs), mmu:16532 (Mm), rno:680912 (Rn)
OMIM 615215 (Hs)
Pharos A8MYU2 (Hs)
RefSeq Nucleotide NM_001031836 (Hs), NM_008432 (Mm)
RefSeq Protein NP_001027006 (Hs), NP_032458 (Mm)
UniProtKB A8MYU2 (Hs), O54982 (Mm)
Wikipedia KCNU1 (Hs)
Functional Characteristics Click here for help
Sperm pH-regulated K+ current, KSPER
Ion Selectivity and Conductance Click here for help
Species:  Human
Rank order:  K+ [106.0 - 110.0 pS] > Na+
References:  5,12
Voltage Dependence Click here for help
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  170.0 10.0 – 1.0 11 Xenopus laevis oocyte Mouse
Inactivation  - -
Comments  V0.5 of activation decreases with increasing pH, saturating for pH>8.0. Activation kinetics can be describes as the weighted sum of two exponentials (tau,slow=10 msec; tau,fast=1.0 msec), with the relative proportion of tau,fast increasing with increasing pH.

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Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
NS004 Small molecule or natural product Click here for species-specific activity table Hs - - - - -
⤷
NS1619 Small molecule or natural product Click here for species-specific activity table Hs - - - - -
⤷
Activator Comments
Increase in (-OH) or pH can modulate mSlo3 activation: When expressed in the Xenopus oocyte expression system, mSlo3 cRNA produced currents that were sensitive to both pH and voltage. Currents are sensitive to intracellular pH. Currents were small or absent at a pH of 7.1 or lower, whereas raising pH (to >= 7.5) resulted in sharp increases in channel activity. The effect of changing pH was shown to be completely and repeatedly reversible [5,11].
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
quinidine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Hs - - - < 1x10-4 - 7
⤷ Conc range: < 1x10-4 M [7]
quinidine Small molecule or natural product Approved drug Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Mm - - - 2x10-5 - 8-9
⤷ Conc range: 2x10-5 M [8-9]
View species-specific channel blocker tables
Tissue Distribution Click here for help
Testis
Species:  Human
Technique:  Northern Blot
References:  5
Spermatocytes
Species:  Mouse
Technique:  In situ hybridisation
References:  5
Testis
Species:  Mouse
Technique:  RT-PCR
References:  5
Physiological Functions Click here for help
KCNU1 may encode a large-conductance potassium channel (dubbed KSper) activated by both voltage and internal alkalinization, recorded from mature sperm. This channel is thought to underlie a pH-triggered membrane hyperpolarization observed during the process of sperm capacitation, as sperm encounter the alkaline environment near the ovum in the female reproductive tract. Normal capacitation is required for sperm to become fully competent for fertilization. In mice, the consensus is that this current is encoded by KCNU1. In human sperm, an initial report attributed KSper to KCNMA1 based on recordings of native currents from human sperm, which exhibit activation primary by internal Ca2+ and a pharmacological profile consistent with KCNMA1. A more recent study, however concludes that the human KSper-like current is in fact encoded by human KCNU1, analogous to mouse sperm. The explanation for this apparent contradiction offered by this study is that channels encoded by the human KCNU1 gene are functionally different from those encoded by the mouse ortholog. Despite strong sequence similarity, human KCNU1 channels are significantly more sensitive to activation by internal Ca2+ and less pH-sensitive than mouse KCNU1, which makes them functionally similar to typical KCNMA1 channels.
Species:  Mouse
Tissue:  Sperm
References:  1,3-4,10
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcnu1tm1Cmsa Kcnu1tm1Cmsa/Kcnu1tm1Cmsa
Not Specified		 MGI:1202300  MP:0002675 asthenozoospermia PMID: 20138882 
Kcnu1tm1Cmsa Kcnu1tm1Cmsa/Kcnu1tm1Cmsa
Not Specified		 MGI:1202300  MP:0004542 impaired acrosome reaction PMID: 20138882 
Kcnu1tm1Cmsa Kcnu1tm1Cmsa/Kcnu1tm1Cmsa
Not Specified		 MGI:1202300  MP:0000242 impaired fertilization PMID: 20138882 
Kcnu1tm1Cmsa Kcnu1tm1Cmsa/Kcnu1tm1Cmsa
Not Specified		 MGI:1202300  MP:0003666 impaired sperm capacitation PMID: 20138882 
Kcnu1tm1Cmsa Kcnu1tm1Cmsa/Kcnu1tm1Cmsa
Not Specified		 MGI:1202300  MP:0001925 male infertility PMID: 20138882 

References

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1. Brenker C, Zhou Y, Müller A, Echeverry FA, Trötschel C, Poetsch A, Xia XM, Bönigk W, Lingle CJ, Kaupp UB et al.. (2014) The Ca2+-activated K+ current of human sperm is mediated by Slo3. Elife, 3: e01438. [PMID:24670955]

2. Gibbs RA, Weinstock GM, Metzker ML, Muzny DM, Sodergren EJ, Scherer S, Scott G, Steffen D, Worley KC, Burch PE et al.. (2004) Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature, 428 (6982): 493-521. [PMID:15057822]

3. Navarro B, Kirichok Y, Clapham DE. (2007) KSper, a pH-sensitive K+ current that controls sperm membrane potential. Proc Natl Acad Sci USA, 104 (18): 7688-92. [PMID:17460039]

4. Santi CM, Martínez-López P, de la Vega-Beltrán JL, Butler A, Alisio A, Darszon A, Salkoff L. (2010) The SLO3 sperm-specific potassium channel plays a vital role in male fertility. FEBS Lett, 584 (5): 1041-6. [PMID:20138882]

5. Schreiber M, Wei A, Yuan A, Gaut J, Saito M, Salkoff L. (1998) Slo3, a novel pH-sensitive K+ channel from mammalian spermatocytes. J Biol Chem, 273 (6): 3509-16. [PMID:9452476]

6. Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF et al.. (2002) Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proc Natl Acad Sci USA, 99 (26): 16899-903. [PMID:12477932]

7. Sánchez-Carranza O, Torres-Rodríguez P, Darszon A, Treviño CL, López-González I. (2015) Pharmacology of hSlo3 channels and their contribution in the capacitation-associated hyperpolarization of human sperm. Biochem Biophys Res Commun, 466 (3): 554-9. [PMID:26381170]

8. Tang QY, Zhang Z, Xia XM, Lingle CJ. (2010) Block of mouse Slo1 and Slo3 K+ channels by CTX, IbTX, TEA, 4-AP and quinidine. Channels (Austin), 4 (1): 22-41. [PMID:19934650]

9. Wrighton DC, Muench SP, Lippiat JD. (2015) Mechanism of inhibition of mouse Slo3 (KCa 5.1) potassium channels by quinine, quinidine and barium. Br J Pharmacol, 172 (17): 4355-63. [PMID:26045093]

10. Zeng XH, Yang C, Kim ST, Lingle CJ, Xia XM. (2011) Deletion of the Slo3 gene abolishes alkalization-activated K+ current in mouse spermatozoa. Proc Natl Acad Sci USA, 108 (14): 5879-84. [PMID:21427226]

11. Zhang X, Zeng X, Lingle CJ. (2006) Slo3 K+ channels: voltage and pH dependence of macroscopic currents. J Gen Physiol, 128 (3): 317-36. [PMID:16940555]

12. Zhang X, Zeng X, Xia XM, Lingle CJ. (2006) pH-regulated Slo3 K+ channels: properties of unitary currents. J Gen Physiol, 128 (3): 301-15. [PMID:16940554]

Contributors

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