Kir6.2-deficient mice develop somatosensory dysfunction and axonal loss in the peripheral nerves

Area of Science:

• Neuroscience
• Physiology
• Molecular Biology

Background:

• Glucose-responsive ATP-sensitive potassium channels (KATP) are found in various tissues, including nervous systems.
• The role of KATP channels in the peripheral nervous system (PNS) remains largely unknown.
• Neuronal depolarization by glucose can lead to hyperexcitability and excitotoxicity.

Purpose of the Study:

• To investigate the function of KATP channels in the peripheral nervous system.
• To determine the involvement of KATP channels in peripheral neuropathy.

Main Methods:

• Utilized KATP-deficient (Kir6.2-deficient) mice for experiments.
• Assessed neurite outgrowth using channel modulators (sulfonylureas and diazoxide).
• Examined KATP subunit expression in dorsal root ganglion (DRG) neurons, including in diabetic models.
• Evaluated sensory perception thresholds and nerve conduction velocity in Kir6.2-deficient mice.
• Performed electron microscopy on sural nerves to analyze nerve fiber morphology.

Main Results:

• Sulfonylureas reduced, while diazoxide elongated, neurite outgrowth of DRG neurons.
• KATP subunits, including Kir6.2, were expressed in mouse DRG and upregulated in diabetic mice.
• Kir6.2-deficient mice exhibited impaired sensory perception and reduced nerve conduction velocity.
• Sural nerve analysis revealed fewer unmyelinated and small myelinated fibers in Kir6.2-deficient mice.

Conclusions:

• KATP channels are present and functional in the peripheral nervous system.
• KATP channel dysfunction is associated with peripheral nerve deficits.
• KATP channels are implicated in the pathogenesis of peripheral neuropathy.