Peripheral K_V7 channels regulate visceral sensory function in mouse and human colon.

Area of Science:

• Neuroscience
• Gastroenterology
• Pharmacology

Background:

• Chronic visceral pain is a significant symptom in many gastrointestinal disorders.
• Voltage-gated potassium channels (K_V7.1-K_V7.5) are crucial for regulating neuronal excitability in pain pathways.
• Peripheral K_V7 channels' role in visceral pain perception requires further investigation.

Purpose of the Study:

• To investigate the contribution of peripheral K_V7 channels to visceral nociception using mouse and human tissues.
• To explore the expression and function of K_V7 channel subtypes in gut-innervating sensory neurons.

Main Methods:

• Immunohistochemistry to identify K_V7 subtypes in mouse and human colon.
• Gut-nerve electrophysiological recordings to assess visceral afferent firing.
• Single-cell real-time polymerase chain reaction to analyze gene expression in sensory neurons.
• Pharmacological manipulation using K_V7 opener (retigabine) and blocker (XE991).

Main Results:

• K_V7.3 and K_V7.5 subtypes were found in enteric neurons and sensory fibers in the mouse colon.
• Retigabine significantly inhibited bradykinin-evoked visceral afferent firing and attenuated responses to mechanical stimulation.
• K_V7 channel expression and function were confirmed in human colon tissues, with retigabine inhibiting bradykinin-induced afferent activation.

Conclusions:

• K_V7 channels play a critical role in the sensitivity of visceral sensory neurons to noxious stimuli.
• Peripherally restricted K_V7 channel openers show therapeutic potential for gastrointestinal pain conditions.