Differential regulation of proton-sensitive ion channels by phospholipids: a comparative study between ASICs and TRPV1

PloS One
Hae-Jin KweonByung-Chang Suh

Abstract

Protons are released in pain-generating pathological conditions such as inflammation, ischemic stroke, infection, and cancer. During normal synaptic activities, protons are thought to play a role in neurotransmission processes. Acid-sensing ion channels (ASICs) are typical proton sensors in the central nervous system (CNS) and the peripheral nervous system (PNS). In addition to ASICs, capsaicin- and heat-activated transient receptor potential vanilloid 1 (TRPV1) channels can also mediate proton-mediated pain signaling. In spite of their importance in perception of pH fluctuations, the regulatory mechanisms of these proton-sensitive ion channels still need to be further investigated. Here, we compared regulation of ASICs and TRPV1 by membrane phosphoinositides, which are general cofactors of many receptors and ion channels. We observed that ASICs do not require membrane phosphatidylinositol 4-phosphate (PI(4)P) or phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) for their function. However, TRPV1 currents were inhibited by simultaneous breakdown of PI(4)P and PI(4,5)P2. By using a novel chimeric protein, CF-PTEN, that can specifically dephosphorylate at the D3 position of phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3), ...Continue Reading

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Citations

Jun 21, 2015·European Journal of Cell Biology·Michael G LeitnerDominik Oliver
Jul 28, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Shaherin BasithSun Choi
Apr 24, 2019·The Journal of General Physiology·Jae Seung LeeByung-Chang Suh
Jan 23, 2016·American Journal of Physiology. Cell Physiology·Sonia Martial
Jun 27, 2019·Journal of Neuroscience Research·Chun-Yu QiuWang-Ping Hu
Feb 29, 2020·Acta Pharmacologica Sinica·Lei WuWang-Ping Hu

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