Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 369, Issue 6, pp 602–615

Small and intermediate conductance Ca2+-activated K+ channels confer distinctive patterns of distribution in human tissues and differential cellular localisation in the colon and corpus cavernosum

  • Mao Xiang Chen
  • Shelby A. Gorman
  • Bill Benson
  • Kuljit Singh
  • J. Paul Hieble
  • Martin C. Michel
  • Simon N. Tate
  • Derek J. Trezise
Original Article

DOI: 10.1007/s00210-004-0934-5

Cite this article as:
Chen, M.X., Gorman, S.A., Benson, B. et al. Naunyn-Schmiedeberg's Arch Pharmacol (2004) 369: 602. doi:10.1007/s00210-004-0934-5

Abstract

The SK/IK family of small and intermediate conductance calcium-activated potassium channels contains four members, SK1, SK2, SK3 and IK1, and is important for the regulation of a variety of neuronal and non-neuronal functions. In this study we have analysed the distribution of these channels in human tissues and their cellular localisation in samples of colon and corpus cavernosum. SK1 mRNA was detected almost exclusively in neuronal tissues. SK2 mRNA distribution was restricted but more widespread than SK1, and was detected in adrenal gland, brain, prostate, bladder, liver and heart. SK3 mRNA was detected in almost every tissue examined. It was highly expressed in brain and in smooth muscle-rich tissues including the clitoris and the corpus cavernosum, and expression in the corpus cavernosum was upregulated up to 5-fold in patients undergoing sex-change operations. IK1 mRNA was present in surface-rich, secretory and inflammatory cell-rich tissues, highest in the trachea, prostate, placenta and salivary glands. In detailed immunohistochemical studies of the colon and the corpus cavernosum, SK1-like immunoreactivity was observed in the enteric neurons. SK3-like immunoreactivity was observed strongly in smooth muscle and vascular endothelium. IK1-like immunoreactivity was mainly observed in inflammatory cells and enteric neurons of the colon, but absent in corpus cavernosum. These distinctive patterns of distribution suggest that these channels are likely to have different biological functions and could be specifically targeted for a number of human diseases, such as irritable bowel syndrome, hypertension and erectile dysfunction.

Keywords

Calcium-activated Potassium channel SK IK Colon Penis Corpus cavernosum Smooth muscle Distribution KCNN 

Abbreviations

SK/IK/BK

Small/intermediate/big conductance calcium-activated potassium channels respectively

AHP

Afterhyperpolarisation

EBIO

1-ethyl-2-benzimidazolone

PCR

Polymerase chain reaction

CNS

Central nervous system

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Mao Xiang Chen
    • 1
  • Shelby A. Gorman
    • 2
  • Bill Benson
    • 2
  • Kuljit Singh
    • 3
  • J. Paul Hieble
    • 4
  • Martin C. Michel
    • 5
  • Simon N. Tate
    • 1
  • Derek J. Trezise
    • 6
  1. 1.Gene Expression and Protein BiochemistryGlaxoSmithKline R&DStevenageUK
  2. 2.Quantitative Expression and Genomic HistologyGlaxoSmithKlineUSA
  3. 3.Atherosclerosis CVU CEDDGlaxoSmithKline R&DStevenageUK
  4. 4.Urogenital Biology, CVU CEDDGlaxoSmithKlineKing of PrussiaUSA
  5. 5.Department Pharmacology and PharmacotherapyUniversity of AmsterdamAmsterdamNetherlands
  6. 6.Assay Development and Compound ProfilingGlaxoSmithKline R&DStevenageUK

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