PKD2L1 channels segregated to the apical compartment are the exclusive dual-mode pH sensor in cerebrospinal fluid-contacting neurons
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 t...
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| বিন্যাস: | article |
| ভাষা: | ইংরেজি |
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2026
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| বিষয়গুলি: | |
| অনলাইন ব্যবহার করুন: | https://hdl.handle.net/20.500.12381/5453 https://doi.org/10.7554/eLife.109372 |
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| _version_ | 1868890036129234944 |
|---|---|
| author | Vitar, Magdalena |
| author2 | Prieto, Daniel Malas, Stavros Russo, Raúl E. Trigo, Federico F. |
| author2_role | author author author author |
| author_browse | Malas, Stavros Prieto, Daniel Russo, Raúl E. Trigo, Federico F. Vitar, Magdalena |
| author_facet | Vitar, Magdalena Prieto, Daniel Malas, Stavros Russo, Raúl E. Trigo, Federico F. |
| author_role | author |
| collection | IIBCE en REDI |
| dc.creator.none.fl_str_mv | Vitar, Magdalena Prieto, Daniel Malas, Stavros Russo, Raúl E. Trigo, Federico F. |
| dc.date.none.fl_str_mv | 2026-03-03T12:26:03Z 2026-03-03T12:26:03Z 2026-01-05 |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/20.500.12381/5453 FCE_1_2021_1_166464 https://doi.org/10.7554/eLife.109372 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | eLife |
| dc.relation.none.fl_str_mv | http://doi.org/10.60895/redata/39X8AV https://hdl.handle.net/20.500.12381/4070 https://doi.org/10.60895/redata/ZPXGQ2 |
| dc.rights.none.fl_str_mv | Acceso abierto info:eu-repo/semantics/openAccess Reconocimiento 4.0 Internacional. (CC BY) |
| dc.source.none.fl_str_mv | eLife reponame:IIBCE en REDI instname:Instituto de Investigaciones Biológicas Clemente Estable instacron:Instituto de Investigaciones Biológicas Clemente Estable |
| dc.subject.none.fl_str_mv | neuronas, percepción de pH, PKD2L1, médula espinal Ciencias Médicas y de la Salud Medicina Básica Neurociencias Ciencias Naturales y Exactas Ciencias Biológicas Biología Celular, Microbiología |
| dc.title.none.fl_str_mv | PKD2L1 channels segregated to the apical compartment are the exclusive dual-mode pH sensor in cerebrospinal fluid-contacting neurons |
| dc.type.none.fl_str_mv | Artículo info:eu-repo/semantics/article Aceptado info:eu-repo/semantics/acceptedVersion |
| description | 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | anni_4b677ebec2c3da562b3dffe224e9b5ba |
| identifier_str_mv | FCE_1_2021_1_166464 |
| instacron_str | Instituto de Investigaciones Biológicas Clemente Estable |
| institution | Instituto de Investigaciones Biológicas Clemente Estable |
| instname_str | Instituto de Investigaciones Biológicas Clemente Estable |
| language | eng |
| network_acronym_str | anni |
| network_name_str | oai-lr-anni |
| oai_identifier_str | oai:redi.anii.org.uy:20.500.12381/5453 |
| publishDate | 2026 |
| publishDateSort | 2026 |
| publisher.none.fl_str_mv | eLife |
| reponame_str | IIBCE en REDI |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | Acceso abierto Reconocimiento 4.0 Internacional. (CC BY) |
| spelling | PKD2L1 channels segregated to the apical compartment are the exclusive dual-mode pH sensor in cerebrospinal fluid-contacting neuronsVitar, MagdalenaPrieto, DanielMalas, StavrosRusso, Raúl E.Trigo, Federico F.neuronas, percepción de pH, PKD2L1, médula espinalCiencias Médicas y de la SaludMedicina BásicaNeurocienciasCiencias Naturales y ExactasCiencias BiológicasBiología Celular, MicrobiologíaCerebrospinal 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.Agencia Nacional de Investigación e InnovaciónWings For Life Spinal Cord Research Foundation (number WFL-UY-13/23 #290)eLife2026-03-03T12:26:03Z2026-03-03T12:26:03Z2026-01-05Artículoinfo:eu-repo/semantics/articleAceptadoinfo:eu-repo/semantics/acceptedVersionhttps://hdl.handle.net/20.500.12381/5453FCE_1_2021_1_166464https://doi.org/10.7554/eLife.109372eLifereponame:IIBCE en REDIinstname:Instituto de Investigaciones Biológicas Clemente Estableinstacron:Instituto de Investigaciones Biológicas Clemente Estableenghttp://doi.org/10.60895/redata/39X8AVhttps://hdl.handle.net/20.500.12381/4070https://doi.org/10.60895/redata/ZPXGQ2Acceso abiertoinfo:eu-repo/semantics/openAccessReconocimiento 4.0 Internacional. (CC BY)oai:redi.anii.org.uy:20.500.12381/54532026-06-16T05:25:43Z |
| spellingShingle | PKD2L1 channels segregated to the apical compartment are the exclusive dual-mode pH sensor in cerebrospinal fluid-contacting neurons Vitar, Magdalena neuronas, percepción de pH, PKD2L1, médula espinal Ciencias Médicas y de la Salud Medicina Básica Neurociencias Ciencias Naturales y Exactas Ciencias Biológicas Biología Celular, Microbiología |
| status_str | acceptedVersion |
| title | PKD2L1 channels segregated to the apical compartment are the exclusive dual-mode pH sensor in cerebrospinal fluid-contacting neurons |
| title_full | PKD2L1 channels segregated to the apical compartment are the exclusive dual-mode pH sensor in cerebrospinal fluid-contacting neurons |
| title_fullStr | PKD2L1 channels segregated to the apical compartment are the exclusive dual-mode pH sensor in cerebrospinal fluid-contacting neurons |
| title_full_unstemmed | PKD2L1 channels segregated to the apical compartment are the exclusive dual-mode pH sensor in cerebrospinal fluid-contacting neurons |
| title_short | PKD2L1 channels segregated to the apical compartment are the exclusive dual-mode pH sensor in cerebrospinal fluid-contacting neurons |
| title_sort | PKD2L1 channels segregated to the apical compartment are the exclusive dual-mode pH sensor in cerebrospinal fluid-contacting neurons |
| topic | neuronas, percepción de pH, PKD2L1, médula espinal Ciencias Médicas y de la Salud Medicina Básica Neurociencias Ciencias Naturales y Exactas Ciencias Biológicas Biología Celular, Microbiología |
| url | https://hdl.handle.net/20.500.12381/5453 https://doi.org/10.7554/eLife.109372 |