2021
DOI: 10.3389/fphar.2021.632711
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The Underlying Mechanism of Modulation of Transient Receptor Potential Melastatin 3 by protons

Abstract: Transient receptor potential melastatin 3 channel (TRPM3) is a calcium-permeable nonselective cation channel that plays an important role in modulating glucose homeostasis in the pancreatic beta cells. However, how TRPM3 is regulated under physiological and pathological conditions is poorly understood. In this study, we found that both intracellular and extracellular protons block TRPM3 through its binding sites in the pore region. We demonstrated that external protons block TRPM3 with an inhibitory pH50 of 5.… Show more

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“…Altered acid-base balance can also have a myriad of additional effects, as protons may directly act as neurotransmitters (20) and inflammation-inducing damageassociated molecular patterns (21). Altered brain acidity affects multiple neurological conditions, such as anxiety, possibly through inhibitory action (22) on the TRPM3 ion channel (23), the activity of which is reduced in PASC patients (24), and through activation of acid-sensing ion channels (25). In addition, extracellular acidosis can disrupt the cellular molecular clock (26), potentially affecting circadian rhythms and causing the sleep disturbances often reported by PASC patients (3).…”
Section: Inflammatory Acid-base Disruptions In Pascmentioning
confidence: 99%
“…Altered acid-base balance can also have a myriad of additional effects, as protons may directly act as neurotransmitters (20) and inflammation-inducing damageassociated molecular patterns (21). Altered brain acidity affects multiple neurological conditions, such as anxiety, possibly through inhibitory action (22) on the TRPM3 ion channel (23), the activity of which is reduced in PASC patients (24), and through activation of acid-sensing ion channels (25). In addition, extracellular acidosis can disrupt the cellular molecular clock (26), potentially affecting circadian rhythms and causing the sleep disturbances often reported by PASC patients (3).…”
Section: Inflammatory Acid-base Disruptions In Pascmentioning
confidence: 99%