Urothelial MaxiK-activity regulates mucosal and detrusor metabolism

Yi Wang, Gary G. Deng, Kelvin Davies

Research output: Contribution to journalArticle

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Abstract

There is increasing evidence for a role of MaxiK potassium channel-activity in regulating the metabolism and intracellular signaling of non-contractile bladder mucosal tissues. At present however no studies have determined the impact of urothelial MaxiK-activity on overall bladder metabolism. To address this we have investigated the effect of bladder lumen instillation of the MaxiK inhibitor, iberiotoxin (IBTX), on mucosal and detrusor metabolism using metabolomics. Since IBTX does not cross plasma membranes, when instilled into the bladder lumen it would only effect urothelially expressed MaxiK-activity. Surprisingly IBTX treatment caused more effect on the metabolome of the detrusor than mucosa (the levels of 17% of detected detrusor metabolites were changed in comparison to 6% of metabolites in mucosal tissue following IBTX treatment). In mucosal tissues, the major effects can be linked to mitochondrial-associated metabolism whereas in detrusor there were additional changes in energy generating pathways (such as glycolysis and the TCA cycle). In the detrusor, changes in metabolism are potentially a result of IBTX effecting MaxiK-linked signaling pathways between the mucosa and detrusor, secondary to changes in physiological activity or a combination of both. Overall we demonstrate that urothelial MaxiK-activity plays a significant role in determining mitochondrially-associated metabolism in mucosal tissues, which effects the metabolism of detrusor tissue. Our work adds further evidence that the urothelium plays a major role in determining overall bladder physiology. Since decreased MaxiK-activity is associated with several bladder pathophysiology’s, the changes in mucosal metabolism reported here may represent novel downstream targets for therapeutic interventions.

Original languageEnglish (US)
Article numbere0189387
JournalPLoS One
Volume12
Issue number12
DOIs
StatePublished - Dec 1 2017

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Metabolism
bladder
Mucous Membrane
metabolism
Urinary Bladder
Metabolites
mucosa
metabolites
Large-Conductance Calcium-Activated Potassium Channels
Intravesical Administration
metabolome
Urothelium
Metabolomics
Metabolome
Potassium Channels
potassium channels
Physiology
metabolomics
glycolysis
Glycolysis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Urothelial MaxiK-activity regulates mucosal and detrusor metabolism. / Wang, Yi; Deng, Gary G.; Davies, Kelvin.

In: PLoS One, Vol. 12, No. 12, e0189387, 01.12.2017.

Research output: Contribution to journalArticle

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