TMEM150C Inhibitors

TMEM150C, encoding a transmembrane protein crucial for mechanosensitive ion channels, plays a pivotal role in various cellular processes, including hearing, touch, pain perception, and blood pressure regulation. The gene confers slowly adapting, mechanically activated currents in dorsal root ganglion neurons, highlighting its significance in sensory and physiological functions. TMEM150C's activation relies on mechanical stimuli, making it a key sensor for environmental cues. Inhibition of TMEM150C can be achieved through various mechanisms, either directly or indirectly. Direct inhibitors, such as GsMTx-4, interact with the mechanosensitive ion channel, impeding its activation by disrupting conformational changes induced by mechanical stimuli. Indirect inhibitors, like Ruthenium Red and Gadolinium chloride, interfere with calcium signaling pathways essential for TMEM150C function. Amiloride disrupts sodium-proton exchangers, SKF-96365 blocks store-operated calcium channels, and Dynasore affects endocytosis, all leading to impaired TMEM150C mechanosensitivity.

ML-7 targets myosin light chain kinase, influencing the actin cytoskeleton dynamics crucial for TMEM150C activation. Pyr3 modulates purinergic receptors, Yoda1 hyperactivates alternative channels, and Pyridoxal-5'-phosphate alters pyridoxal kinase-mediated processes. Chlorpromazine affects membrane fluidity, and the Rho kinase inhibitor Y-27632 disrupts the Rho/ROCK pathway, impacting actin cytoskeleton dynamics and, consequently, TMEM150C mechanosensitivity. In summary, understanding TMEM150C's vital role in mechanosensitive ion channels provides a foundation for exploring inhibition strategies.