Pathophysiological Roles of Transient Receptor Potential (Trp) Channels and Zinc Toxicity in Brain Disease

• Type of Material: Article
• Authors: Dae Ki Hong, Hallym University; A Ra Kho, Johns Hopkins University; Song Hee Lee, Hallym University; Beom Seok Kang, Hallym University; Min Kyu Park, Hallym University; Bo Young Choi, Hallym University; Sang Won Suh, Hallym University
• Language: English
• Date: 2023-04-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2023 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/ijms24076665
• Title of Journal or Parent Work: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
• Volume: 24
• Issue: 7
• Keywords: transient receptor potential (TRP) channels; Science & Technology; ION CHANNELS; CATION CHANNEL; HIPPOCAMPAL NEURONAL DEATH; Chemistry; Life Sciences & Biomedicine; Physical Sciences; 2-AMINOETHOXYDIPHENYL BORATE; EPILEPTIFORM ACTIVITY; epilepsy; FUNCTIONAL-CHARACTERIZATION; traumatic brain injury; CELL-DEATH; Chemistry, Multidisciplinary; INTRACEREBRAL HEMORRHAGE; WHITE-MATTER DAMAGE; zinc; ischemic stroke; OPERATED CA2+ ENTRY; Biochemistry & Molecular Biology
• Research Categories: Health Sciences, Pathology

Abstract

Maintaining the correct ionic gradient from extracellular to intracellular space via several membrane-bound transporters is critical for maintaining overall cellular homeostasis. One of these transporters is the transient receptor potential (TRP) channel family that consists of six putative transmembrane segments systemically expressed in mammalian tissues. Upon the activation of TRP channels by brain disease, several cations are translocated through TRP channels. Brain disease, especially ischemic stroke, epilepsy, and traumatic brain injury, triggers the dysregulation of ionic gradients and promotes the excessive release of neuro-transmitters and zinc. The divalent metal cation zinc is highly distributed in the brain and is specifically located in the pre-synaptic vesicles as free ions, usually existing in cytoplasm bound with metallothionein. Although adequate zinc is essential for regulating diverse physiological functions, the brain-disease-induced excessive release and translocation of zinc causes cell damage, including oxidative stress, apoptotic cascades, and disturbances in energy metabolism. Therefore, the regulation of zinc homeostasis following brain disease is critical for the prevention of brain damage. In this review, we summarize recent experimental research findings regarding how TRP channels (mainly TRPC and TRPM) and zinc are regulated in animal brain-disease models of global cerebral ischemia, epilepsy, and traumatic brain injury. The blockade of zinc translocation via the inhibition of TRPC and TRPM channels using known channel antagonists, was shown to be neuroprotective in brain disease. The regulation of both zinc and TRP channels may serve as targets for treating and preventing neuronal death.