Role for TREK-1 as a polymodal sensor and regulator of cell activity - PubMed
5 hours ago
- #therapeutic target
- #mechanotransduction
- #TREK-1 channel
- TREK-1 (KCNK2) is a polymodal two-pore domain potassium channel that integrates mechanical, chemical, and thermal stimuli.
- It regulates resting membrane potential, excitability, and engages in noncanonical signaling via protein interactions and intracellular pathways like MAPK and calcineurin.
- Expressed in the nervous system, TREK-1 influences neuronal firing, pain, mood, and neuroprotection; in the heart, it affects action potential duration, arrhythmias, and stress-induced remodeling.
- In fibroblasts, it acts as a mechanotransducer driving differentiation and fibrosis through MAPK signaling.
- TREK-1 also modulates immune responses, adipogenesis, vascular tone, epithelial injury, and cancer cell proliferation.
- Dysregulation contributes to pathological conditions like excitability, fibrosis, inflammation, and degeneration, making it a promising therapeutic target.