Small and intermediate conductance Ca(2+)-activated K+ channels confer distinctive patterns of distribution in human tissues and differential cellular localisation in the colon and corpus cavernosum.
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.
Chen
Mao Xiang
MX
Gene Expression and Protein Biochemistry, GlaxoSmithKline R&D, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK. mark.x.chen@gsk.com
Gorman
Shelby A
SA
Benson
Bill
B
Singh
Kuljit
K
Hieble
J Paul
JP
Michel
Martin C
MC
Tate
Simon N
SN
Trezise
Derek J
DJ
D000328:Adult; D000368:Aged; D015152:Blotting, Northern; D003106:Colon / Q000098:blood supply / Q000378:metabolism*; D004553:Electric Conductivity; D005260:Female; D005786:Gene Expression Regulation; D005835:Genitalia / Q000098:blood supply / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000098:blood supply / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009928:Organ Specificity; D024681:Potassium Channels, Calcium-Activated / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051640:Small-Conductance Calcium-Activated Potassium Channels
C496894:KCNN1 protein, human; C496897:KCNN2 protein, human; D024681:Potassium Channels, Calcium-Activated; D012333:RNA, Messenger; D051640:Small-Conductance Calcium-Activated Potassium Channels