A pH-sensitive potassium conductance (TASK) and its function in the murine gastrointestinal tract

Area of Science:

• Physiology
• Molecular Biology
• Gastroenterology

Background:

• Smooth muscle excitability relies on background K+ conductances, but known channels don't fully explain resting potentials in GI muscles.
• A significant K+ conductance contributing to resting membrane potential in GI smooth muscles remains unidentified.

Purpose of the Study:

• To identify and characterize novel K+ channels in murine intestinal smooth muscles.
• To investigate the role of these channels in regulating GI smooth muscle excitability and resting membrane potential.

Main Methods:

• Cloning and expression of TASK-2 channels from murine intestinal muscles.
• Whole-cell patch-clamp recordings from native intestinal myocytes.
• Pharmacological characterization using local anesthetics and K+ channel blockers.
• Assessment of effects on circular muscle cells and slow wave activity in intact muscles.

Main Results:

• TASK-2 channels expressed in murine intestinal muscles produce a pH-sensitive, time-dependent, non-inactivating K+ conductance.
• A similar pH-sensitive conductance was identified in native intestinal myocytes.
• Local anesthetics and acidic pH depolarized smooth muscle cells and reduced slow wave activity.
• Lidocaine blocked the effects of acidic pH, indicating involvement of lidocaine-sensitive K+ channels.

Conclusions:

• TASK-1 and TASK-2 genes likely encode the pH-sensitive background K+ conductance in GI muscles.
• This TASK channel-mediated conductance significantly contributes to resting membrane potential.
• These findings suggest TASK channels play a key role in regulating GI smooth muscle excitability.