Function of 10Panx in the pathogenesis of epilepsy

2018-09-21

Introduction 

10Panx is a panx 1 mimetic inhibitor that easily and reversibly inhibits panx1 currents. In cells that are difficult to efficiently and continuously introduce siRNA, 10Panx allows researchers to easily and reversibly detect panx1. Panx1 forms a non-selective, large conductance half channel on the cell membrane. The channel can be opened under the condition of membrane depolarization or mechanical stress, which leads to changes in cell function caused by ion and macromolecular transmembrane flow, thereby mediating the physiological or pathological process of seizure.

Pharmacologic action

10Panx induces epilepsy mainly through the following aspects: (1) ATP release. ATP is an important messenger of intercellular information transmission, which can be released from cells to extracellular space under the action of hypoxia and shear force; (2) Influence Ca2+-ATP. 10Panx is a Ca2+ permeable ion channel. Overexpression of 10Panx can significantly reduce the concentration of Ca2+ in the endoplasmic reticulum and directly spread Ca2+ in adjacent cells. In addition, Cl-transporter blockers can inhibit the activity of 10Panx. Therefore, 10Panx may be involved in the regulation of ion channels; (3) Cause an inflammatory response. Numerous studies have confirmed that cellular inflammation is involved in the development of epilepsy.

Function

10Panx is closely related to N-methyl-Daspartic acid receptors (NMDA receptors) and can be activated by NMDA receptors. The inward current secondary to NMDA receptor activation is due to the opening of the 10Panx channel. Activated 10Panx increases the frequency and amplitude of interphase delivery, and the use of 10Panx specific antagonists can effectively reduce the frequency and amplitude of interphase delivery. Studies on hippocampal slices have found that 10panx significantly reduces the frequency and amplitude of NMDA-induced epileptic discharges and blocks pyramidal neurons from uptake of fluorescent dyes. 10Panx channel plays an important role in epitaxial electrical activity.

Expression of 10Panx

At present, 10Panx has been found to be expressed in tissues such as the eye, cochlea, prostate, thyroid, pituitary, taste bud, and tracheal epithelial cells. The most abundant expression of 10Panx is the nervous system. It is newly discovered that 10Panx is also expressed in the cardiovascular system.

References:

Wang CuiCui et al. Progress of the Role of Panx1 in the Pathogenesis of Epilepsy Chin J Clin Neurosci 2011, 19 (6), 652~656

Nakase, T., & Naus, C. C. (2004). Gap junctions and neurological disorders of the central nervous system. Biochimica Et Biophysica Acta (BBA)-Biomembranes, 1662(1), 149-158.

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