AUTHOR=Pang Vivian Y. , Yang Zhuo , Wu Samuel M. , Pang Ji-Jie 

TITLE=The co-expression of the depolarizing and hyperpolarizing mechanosensitive ion channels in mammalian retinal neurons

JOURNAL=Frontiers in Medicine

VOLUME=11

YEAR=2024

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1463898

DOI=10.3389/fmed.2024.1463898

ISSN=2296-858X

ABSTRACT=<sec id="sec1"><title>Introduction</title><p>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.</p></sec><sec id="sec2"><title>Methods</title><p>Using immunocytochemistry, confocal microscopy, and patch-clamp recording techniques, we studied the co-expression of K<sup>+</sup>-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<sup>2+</sup> than Na<sup>+</sup> (together named N-MSCs), and TRPV4 activity in the mouse retina.</p></sec><sec id="sec3"><title>Results</title><p>TRAAK immunoreactivity (IR) was mainly located in Müller cells. Photoreceptor outer segments (OSs) expressed BK and ENaCα intensively and TRAAK, TRPV2, and TRPV4 weakly. Somas and axons of retinal ganglion cells (RGCs) retrograde-identified clearly expressed ENaCα, 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 (<italic>VSR = 1-noise/signal</italic>) by ~50%, and resulted in ATP crisis, which could inactivate voltage-gated sodium channels in RGCs.</p></sec><sec id="sec4"><title>Conclusion</title><p>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 (<italic>R<sub>K/N</sub></italic> 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.</p></sec>