Key role for Kv11.1 (ether-a-go-go related gene) channels in rat bladder contractility.
Vincenzo BarreseZena WehbeAlice LindenSarah McDowellElizabeth ForresterOleksander PovstyanKaren D McCloskeyIain A GreenwoodPublished in: Physiological reports (2023)
In addition, to their established role in cardiac myocytes and neurons, ion channels encoded by ether-a-go-go-related genes (ERG1-3 or kcnh2,3 and 6) (kcnh2) are functionally relevant in phasic smooth muscle. The aim of the study was to determine the expression and functional impact of ERG expression products in rat urinary bladder smooth muscle using quantitative polymerase chain reaction, immunocytochemistry, whole-cell patch-clamp and isometric tension recording. kcnh2 was expressed in rat bladder, whereas kcnh6 and kcnh3 expression were negligible. Immunofluorescence for the kcnh2 expression product Kv11.1 was detected in the membrane of isolated smooth muscle cells. Potassium currents with voltage-dependent characteristics consistent with Kv11.1 channels and sensitive to the specific blocker E4031 (1 μM) were recorded from isolated detrusor smooth muscles. Disabling Kv11.1 activity with specific blockers (E4031 and dofetilide, 0.2-20 μM) augmented spontaneous contractions to a greater extent than BK Ca channel blockers, enhanced carbachol-driven activity, increased nerve stimulation-mediated contractions, and impaired β-adrenoceptor-mediated inhibitory responses. These data establish for the first time that Kv11.1 channels are key determinants of contractility in rat detrusor smooth muscle.
Keyphrases
- smooth muscle
- poor prognosis
- oxidative stress
- image quality
- angiotensin converting enzyme
- stem cells
- long non coding rna
- magnetic resonance imaging
- gene expression
- electronic health record
- ionic liquid
- genome wide
- high resolution
- cell therapy
- angiotensin ii
- deep learning
- artificial intelligence
- botulinum toxin
- virtual reality