PKD2L1 channels segregated to the apical compartment are the dual-mode pH sensor in cerebrospinal fluid-contacting neurons.

Authors

Magdalena Vitar, Daniel Prieto, Stavros Malas, Raúl E Russo, Federico F Trigo

Published in

eLife. Volume 15. Sep 29, 2026. Epub Sep 29, 2026.

Abstract

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 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 sustained 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.

PMID:
42809452
Bibliographic data and abstract were imported from PubMed on 30 Sep 2026.

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