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ORIGINAL RESEARCH article

Front. Med.
Sec. Ophthalmology
Volume 11 - 2024 | doi: 10.3389/fmed.2024.1463898
This article is part of the Research Topic The Role of Calcium Channels in Human Health and Disease Volume III View all articles

The co-expression of the depolarizing and hyperpolarizing mechanosensitive ion channels in mammalian retinal neurons Runing title: Co-expression of MSCs in retinal neurons

Provisionally accepted
Vivian Pang Vivian Pang Zhuo Yang Zhuo Yang Samuel Wu Samuel Wu Ji-Jie Pang Ji-Jie Pang *
  • Department of Ophthalmology, Baylor College of Medicine, Houston, Ohio, United States

The final, formatted version of the article will be published soon.

    Introduction: The elevation of the intraocular and extraocular pressures is associated with various visual conditions, including glaucoma and traumatic retinal injury. The retina expresses mechanosensitive channels (MSCs), but the role of MSCs in retinal physiology and pathologies has been unclear. Methods: Using immunocytochemistry, confocal microscopy, and patch clamp recording techniques, we studied the co-expression of K + -permeable (K-MSCs) TRAAK and big potassium channel BK with the epithelial sodium channel ENaC and transient receptor potential channel vanilloid TPRV4 and TRPV2 favorably permeable to Ca 2+ than Na + (together named N-MSCs), and TRPV4 activity in the mouse retina. Results: TRAAK immunoreactivity (IR) was mainly located in Müller cells. Photoreceptor outer segments (OSs) expressed BK and ENaCalpha intensively and TRAAK, TRPV2, and TRPV4 weakly. Somas and axons of retinal ganglion cells (RGCs) retrograde-identified clearly expressed ENaCalpha, TRPV4, and TRPV2 but lacked TRAAK and BK. Rod bipolar cells (RBCs) showed TRPV4-IR in somas and BK-IR in axonal globules. Horizontal cells were BK-negative, and some cone BCs lacked TRPV4-IR. TRPV4 agonist depolarized RGCs, enhanced spontaneous spikes and excitatory postsynaptic currents, reduced the visual signal reliability (VSR=1-noise/signal) by ~50%, and resulted in ATP crisis, which could inactivate voltage-gated sodium channels in RGCs. Conclusions: Individual neurons co-express hyperpolarizing K-MSCs with depolarizing N-MSCs to counterbalance the pressure-induced excitation, and the level of K-MSCs relative to N-MSCs (RK/N ratio) is balanced in the outer retina but low in RGCs, bringing out novel determinants for the pressure vulnerability of retinal neurons and new targets for clinical interventions.

    Keywords: TRAAK, BK, TRPV2, TRPV4, ENaC, immunocytochemistry, confocal microscopy, Whole-cell patch-clamp

    Received: 17 Jul 2024; Accepted: 25 Sep 2024.

    Copyright: © 2024 Pang, Yang, Wu and Pang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ji-Jie Pang, Department of Ophthalmology, Baylor College of Medicine, Houston, 77030, Ohio, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.