Padilla-Flores 2020 Biochem Biophys Res Commun
|Padilla-Flores T, Lopez-Gonzalez Z, Vaca L, Aparicio-Trejo OE, Briones-Herrera A, Riveros-Rosas H, Pedraza-Chaverri J, Leon-Aparicio D, Salvador C, Sampieri A, Escobar LI (2020) "Funny" channels in cardiac mitochondria modulate membrane potential and oxygen consumption. Biochem Biophys Res Commun 524:1030-36.|
Padilla-Flores T, Lopez-Gonzalez Z, Vaca L, Aparicio-Trejo OE, Briones-Herrera A, Riveros-Rosas H, Pedraza-Chaverri J, Leon-Aparicio D, Salvador C, Sampieri A, Escobar LI (2020) Biochem Biophys Res Commun
Abstract: The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are encoded by a family of four genes (HCN1-4). All isoforms are expressed in the heart, HCN4 being the most abundant in the sinoatrial node (SAN). HCN channels are responsible for the "funny" current (If) associated with the generation and autonomic control of the diastolic depolarization phase of cardiac action potential. In this work we performed a proteomic analysis of HCN4 transfected in HEK293 cells. Most of the identified proteins in the HCN4 network belonged to mitochondria. The subcellular localization of HCN channels was predicted in plasma membrane, mitochondria and nucleus. Experimentally, HCN2 (full-length, truncated), HCN3 (full-length, truncated) and HCN4 (truncated) were detected in rat heart mitochondria by immunoblotting. If sensitive to ZD7288, was recorded by patch-clamp in mitoplasts from cardiomyocytes. Mitochondrial membrane potential (ΔΨm) assessment in H9c2 cells revealed that ZD7288 induced almost 50% higher hyperpolarization respect to control at 30 min. Furthermore, ZD7288 reduced oxygen consumption attributed to ATP synthesis in H9c2 cells. In conclusion, we identify for the first time functional HCN channels in mammalian cardiac mitochondria and demonstrate their impact on ΔΨm and respiration.
Copyright © 2020 Elsevier Inc. All rights reserved.
Labels: MiParea: Respiration, mt-Membrane
Organism: Rat Tissue;cell: Heart Preparation: Intact cells
Coupling state: LEAK, ROUTINE Pathway: ROX HRR: Oxygraph-2k