Novel Potassium Channels in Kidney Mitochondria: The Hyperpolarization-Activated and Cyclic Nucleotide-Gated HCN Channels
Hyperpolarization-activated cationic HCN channels comprise four members (HCN1–4) that control dendritic integration, synaptic transmission and action potential firing. In the kidney, HCN1, HCN2 and HCN3 are differentially expressed and contribute to the transport of sodium, potassium (K(+)) and ammo...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834191/ https://www.ncbi.nlm.nih.gov/pubmed/31601020 http://dx.doi.org/10.3390/ijms20204995 |
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author | León-Aparicio, Daniel Salvador, Carolina Aparicio-Trejo, Omar Emiliano Briones-Herrera, Alfredo Pedraza-Chaverri, José Vaca, Luis Sampieri, Alicia Padilla-Flores, Teresa López-González, Zinaeli León-Contreras, Juan C Hernández-Pando, Rogelio Escobar, Laura I |
author_facet | León-Aparicio, Daniel Salvador, Carolina Aparicio-Trejo, Omar Emiliano Briones-Herrera, Alfredo Pedraza-Chaverri, José Vaca, Luis Sampieri, Alicia Padilla-Flores, Teresa López-González, Zinaeli León-Contreras, Juan C Hernández-Pando, Rogelio Escobar, Laura I |
author_sort | León-Aparicio, Daniel |
collection | PubMed |
description | Hyperpolarization-activated cationic HCN channels comprise four members (HCN1–4) that control dendritic integration, synaptic transmission and action potential firing. In the kidney, HCN1, HCN2 and HCN3 are differentially expressed and contribute to the transport of sodium, potassium (K(+)) and ammonium into the nephrons. HCN3 is regulated by K(+) diets in the kidney. In this work we performed a proteomic analysis of HCN3 expressed in human embryonic kidney cells (HEK293 cells). More than 50% of the interacting proteins belonged to mitochondria. Therefore, we explored the presence of HCN channels in kidney mitochondria. By immunoblotting and immunogold electron microscopy HCN3 protein expression was found in rat kidney mitochondria; it was also confirmed in human kidney. Patch-clamp recordings of renal mitochondria and mitochondria from HEK293 cells overexpressing HCN1, HCN2 and HCN3 channels, stained with MitoTracker Green FM, indicated that only HCN3 could produce inwardly K(+) currents that were inhibited by ZD7288, a specific blocker of HCN channels. Furthermore, ZD7288 caused inhibition of the oxygen consumption coupled to ATP synthesis and hyperpolarization of the inner mitochondrial membrane. In conclusion, we show for the first time that pacemaker HCN channels contribute to K(+) transport in mitochondria facilitating the activity of the respiratory chain and ATP synthesis by controlling the inner mitochondrial membrane potential. |
format | Online Article Text |
id | pubmed-6834191 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68341912019-11-25 Novel Potassium Channels in Kidney Mitochondria: The Hyperpolarization-Activated and Cyclic Nucleotide-Gated HCN Channels León-Aparicio, Daniel Salvador, Carolina Aparicio-Trejo, Omar Emiliano Briones-Herrera, Alfredo Pedraza-Chaverri, José Vaca, Luis Sampieri, Alicia Padilla-Flores, Teresa López-González, Zinaeli León-Contreras, Juan C Hernández-Pando, Rogelio Escobar, Laura I Int J Mol Sci Article Hyperpolarization-activated cationic HCN channels comprise four members (HCN1–4) that control dendritic integration, synaptic transmission and action potential firing. In the kidney, HCN1, HCN2 and HCN3 are differentially expressed and contribute to the transport of sodium, potassium (K(+)) and ammonium into the nephrons. HCN3 is regulated by K(+) diets in the kidney. In this work we performed a proteomic analysis of HCN3 expressed in human embryonic kidney cells (HEK293 cells). More than 50% of the interacting proteins belonged to mitochondria. Therefore, we explored the presence of HCN channels in kidney mitochondria. By immunoblotting and immunogold electron microscopy HCN3 protein expression was found in rat kidney mitochondria; it was also confirmed in human kidney. Patch-clamp recordings of renal mitochondria and mitochondria from HEK293 cells overexpressing HCN1, HCN2 and HCN3 channels, stained with MitoTracker Green FM, indicated that only HCN3 could produce inwardly K(+) currents that were inhibited by ZD7288, a specific blocker of HCN channels. Furthermore, ZD7288 caused inhibition of the oxygen consumption coupled to ATP synthesis and hyperpolarization of the inner mitochondrial membrane. In conclusion, we show for the first time that pacemaker HCN channels contribute to K(+) transport in mitochondria facilitating the activity of the respiratory chain and ATP synthesis by controlling the inner mitochondrial membrane potential. MDPI 2019-10-09 /pmc/articles/PMC6834191/ /pubmed/31601020 http://dx.doi.org/10.3390/ijms20204995 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article León-Aparicio, Daniel Salvador, Carolina Aparicio-Trejo, Omar Emiliano Briones-Herrera, Alfredo Pedraza-Chaverri, José Vaca, Luis Sampieri, Alicia Padilla-Flores, Teresa López-González, Zinaeli León-Contreras, Juan C Hernández-Pando, Rogelio Escobar, Laura I Novel Potassium Channels in Kidney Mitochondria: The Hyperpolarization-Activated and Cyclic Nucleotide-Gated HCN Channels |
title | Novel Potassium Channels in Kidney Mitochondria: The Hyperpolarization-Activated and Cyclic Nucleotide-Gated HCN Channels |
title_full | Novel Potassium Channels in Kidney Mitochondria: The Hyperpolarization-Activated and Cyclic Nucleotide-Gated HCN Channels |
title_fullStr | Novel Potassium Channels in Kidney Mitochondria: The Hyperpolarization-Activated and Cyclic Nucleotide-Gated HCN Channels |
title_full_unstemmed | Novel Potassium Channels in Kidney Mitochondria: The Hyperpolarization-Activated and Cyclic Nucleotide-Gated HCN Channels |
title_short | Novel Potassium Channels in Kidney Mitochondria: The Hyperpolarization-Activated and Cyclic Nucleotide-Gated HCN Channels |
title_sort | novel potassium channels in kidney mitochondria: the hyperpolarization-activated and cyclic nucleotide-gated hcn channels |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834191/ https://www.ncbi.nlm.nih.gov/pubmed/31601020 http://dx.doi.org/10.3390/ijms20204995 |
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