Expression and function of K(V)2-containing channels in human urinary bladder smooth muscle
Kiril L Hristov1, Muyan Chen, Serge A Y Afeli
1Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, 29208, USA.
American Journal of Physiology. Cell Physiology
|March 17, 2012
Summary
Voltage-gated potassium (K(V)) channels, specifically K(V)2-containing channels, regulate human detrusor smooth muscle (DSM) function. Inhibiting these channels increases DSM excitability and contractility, suggesting new therapeutic targets for bladder dysfunction.
Area of Science:
- Physiology
- Pharmacology
- Molecular Biology
Background:
- The role of voltage-gated potassium (K(V)) channels in human detrusor smooth muscle (DSM) function remains largely uncharacterized.
- Understanding these channels is crucial for addressing bladder dysfunction.
Purpose of the Study:
- To investigate the presence and function of K(V)2.1, K(V)2.2, and K(V)9.3 subunits in human DSM.
- To determine the impact of K(V)2-containing channels on DSM excitability and contractility.
Main Methods:
- RT-PCR and immunocytochemistry to detect K(V) subunit expression in human DSM cells.
- Perforated whole-cell patch-clamp to measure K(V) currents and intracellular calcium.
- Isometric tension recordings to assess DSM contractility in response to ScTx1.
Main Results:
- K(V)2.1, K(V)2.2, and K(V)9.3 mRNA and protein were detected in human DSM.
- Stromatoxin-1 (ScTx1), a K(V)2 inhibitor, reduced K(V) currents and increased intracellular Ca(2+) in DSM cells.
- ScTx1 enhanced spontaneous and stimulated DSM contractions, indicating increased excitability.
Conclusions:
- ScTx1-sensitive K(V)2-containing channels are key regulators of human DSM excitability and contractility.
- These channels represent potential therapeutic targets for managing bladder dysfunction.
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