Daniel PrietoHi #ScienceMastodon , today I'm happy to share our latest preprint by Vitar et al. on @biorxivpreprint
Some fresh and really cool findings about a specialized dendritic subdomain of cerebrospinal fluid-contacting neurons of the spinal cord. A new transgenic, lots of physiology experiments, and so on.
"PH sensitivity of cerebrospinal fluid-contacting neurons involves the modulation of phasic and tonic currents mediated by PKD2L1 channels located in the apical process."
https://www.biorxiv.org/content/10.1101/2025.08.24.671961v1
@SocNeuroUy #neuroscience #neurons #spinalcord #Uruguay #science #neuro #cells #physiology #physiologie #research #biology #iibce
PH sensitivity of cerebrospinal fluid-contacting neurons involves the modulation of phasic and tonic currents mediated by PKD2L1 channels located in the apical process.
Cerebrospinal fluid contacting neurons (CSFcNs) are GABAergic cells that surround the central canal (CC) of the spinal cord. Their soma is located sub-ependymally and they have a dendritic-like process that ends as a bulb (the so-called apical process; ApPr) inside the CC. It remains unclear how this unique anatomical organization, with the soma and the ApPr located in different extracellular environments, relates to their function as a multimodal sensor of cerebrospinal fluid (CSF) composition. One of the main physiological features of CSFcNs is a prominent spontaneous electrical activity mediated by PKD2L1 (or TRPP2) channels, a non-selective cation channel of the TRP family. PKD2L1 channels have a high single-channel conductance (around 200 pS) and can be modulated by protons and mechanical forces. In this work we investigate PKD2L1 channel sensitivity to pH and its effects on CSFcNs excitability. We demonstrate that PKD2L1 spontaneous activity generates not only phasic inward currents, but also a tonic current, both of which are modulated bidirectionally by pH with a high sensitivity around physiological values. By combining electrophysiology (direct recordings from intact and isolated ApPrs) with optical methods (laser-photolysis of protons) we further show that functional PKD2L1 channels are specifically localized in the ApPr. The spatial segregation of PKD2L1 channels, along with their biophysical properties (high single-channel conductance and pH sensitivity) and the ApPr's unique membrane properties (very high input resistance) renders CSFcN excitability exquisitely sensitive to PKD2L1 modulation. Altogether, our findings illustrate how the ApPr's properties are finely tuned to support its sensory role. ### Competing Interest Statement The authors have declared no competing interest. Agencia Nacional de Investigación e Innovación, FCE\_1\_2021\_1\_166464 Wings For Life Spinal Cord Research Foundation, WFL-UY-13/23 #290
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