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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

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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.

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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

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Acknowledgments

We would like to thank Dr. Chris Plumpton and Mrs. Amanda Jowett for preparing the antibodies, and Dr. Susanne Krege for providing the corpus cavernosum tissues.

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Authors and Affiliations

  1. Gene Expression and Protein Biochemistry, GlaxoSmithKline R&D, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK

    Mao Xiang Chen & Simon N. Tate

  2. Quantitative Expression and Genomic Histology, GlaxoSmithKline, Research Triangle Park, NC 27709, USA

    Shelby A. Gorman & Bill Benson

  3. Atherosclerosis CVU CEDD, GlaxoSmithKline R&D, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK

    Kuljit Singh

  4. Urogenital Biology, CVU CEDD, GlaxoSmithKline, Upper Merion, 709 Swedeland Road, King of Prussia, Pennsylvania, 19406, USA

    J. Paul Hieble

  5. Department Pharmacology and Pharmacotherapy, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, Netherlands

    Martin C. Michel

  6. Assay Development and Compound Profiling, GlaxoSmithKline R&D, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK

    Derek J. Trezise

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  1. Mao Xiang Chen
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Correspondence to Mao Xiang Chen.

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Chen, M.X., Gorman, S.A., Benson, B. et al. 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. Naunyn-Schmiedeberg's Arch Pharmacol 369, 602–615 (2004). https://doi.org/10.1007/s00210-004-0934-5

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