Two pore domain THIK2 potassium channels regulate acute and chronic pain signaling
Abstract
Introduction: Two-pore domain potassium channels regulate neuronal excitability by generating background potassium currents that stabilize the resting membrane potential. Although several two-pore domain potassium channels have been implicated in pain signaling, the physiological role of tandem pore domain halotane-inhibited K+ channel (THIK2) remains largely unknown despite its high expression in human and mouse nociceptive dorsal root ganglion (DRG) neurons.
Objective: This study aimed to determine the cellular distribution of THIK2 in sensory neurons and to investigate its contribution to neuronal excitability and nociceptive processing under physiological and inflammatory conditions.
Methods: We combined molecular analyses, electrophysiological recordings, and behavioral approaches. THIK1 and THIK2 expression patterns were mapped in mouse DRGs. Whole-cell electrophysiology was used to assess membrane excitability in sensory neurons from wild-type and THIK2-/- knockout mice. Behavioral tests evaluated thermal sensitivity under naive and inflammatory conditions.
Results: We provide the first comprehensive characterization of THIK1 and THIK2 expression in mouse DRG. THIK2 deletion increased neuronal firing during sustained stimulation, indicating a loss of tonic inhibitory control of membrane excitability, particularly in nonpeptidergic IB4-positive C-fiber neurons. Behaviorally, THIK2-/- mice displayed marked thermal hypersensitivity at baseline and during inflammation,…
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