TRPV4 mediates flow-induced increases in intracellular Ca in medullary thick ascending limbs

Acta Physiologica
Pablo D CabralJ L Garvin

Abstract

Medullary thick ascending limbs (mTAL) regulate Na balance and therefore blood pressure. We previously showed that cell swelling and luminal flow activates the mechanosensitive channel TRPV4 in mTAL. We hypothesized that TRPV4 mediates flow-induced increases in intracellular Ca (Cai) in rat mTALs. We performed ratiometric measurements of Cai in perfused mTALs. Increasing luminal flow from 0 to 20 nL min(-1) caused Cai to peak 231 ± 29 nmol L(-1) above basal concentrations (n = 18). The general TRPV inhibitor ruthenium red at 15 and 50 μmol L(-1) reduced peak Cai by 41 ± 9 (P < 0.01; n = 5) and 77 ± 10% (P < 0.02; n = 6). The selective TRPV4 inhibitor RN1734 at 10 and 50 μmol L(-1) reduced peak Cai by 46 ± 11 (P < 0.01; n = 7) and 76 ± 5% (P < 0.02; n = 5) respectively. To specifically target TRPV4, mTALs were transduced with adenoviruses expressing TRPV4 small hairpin (sh) RNA. In non-transduced control mTALs, luminal flow generated a peak increase in Cai of 111 ± 21 nmol L(-1) (n = 8). In TRPV4shRNA-transduced mTALs, the Cai peak was reduced to 56 ± 8 nmol L(-1) (P < 0.03, n = 9). Removing extracellular Ca completely abolished flow-induced increases in Cai. Increasing luminal flow in the presence of hexokinase 20 (U mL(-1) ) t...Continue Reading

References

Mar 1, 1979·Circulation Research·W J Arendshorst
May 1, 1990·The American Journal of Physiology·N H Holstein-Rathlou, D J Marsh
Nov 1, 1982·Kidney International·M B Burg
Mar 17, 2001·Proceedings of the National Academy of Sciences of the United States of America·S González-PerrettH F Cantiello
Apr 9, 2001·American Journal of Physiology. Renal Physiology·Craig WodaLisa M Satlin
Nov 1, 2001·The Journal of Membrane Biology·Helle A Praetorius, K R Spring
Aug 9, 2002·American Journal of Physiology. Renal Physiology·Craig WodaLisa M Satlin
Feb 7, 2003·The Journal of Membrane Biology·Helle A PraetoriusK R Spring
Mar 13, 2003·Kidney International·P A OrtizJ L Garvin
Jun 26, 2003·American Journal of Physiology. Renal Physiology·Craig WodaLisa M Satlin
Jul 3, 2003·American Journal of Physiology. Renal Physiology·Wen LiuLisa M Satlin
Aug 16, 2003·Current Opinion in Nephrology and Hypertension·S C Hebert
Sep 1, 2004·Biochemical and Biophysical Research Communications·Georgia I Anyatonwu, Barbara E Ehrlich
May 24, 2005·Pflügers Archiv : European journal of physiology·Roger G O'Neil, Stefan Heller
Apr 28, 2006·American Journal of Physiology. Renal Physiology·Tetsuji MorimotoThomas R Kleyman
May 6, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Ralf KöhlerJoachim Hoyer
Sep 7, 2006·American Journal of Physiology. Renal Physiology·Junichi TaniguchiMakoto Suzuki
Jun 8, 2007·Journal of the American Society of Nephrology : JASN·Mikkel Erik Juul JensenJens Leipziger
Aug 19, 2007·American Journal of Physiology. Renal Physiology·Ling WuRoger G O'Neil
Sep 6, 2007·PloS One·Veronika HartmannsgruberRalf Köhler
Jan 29, 2008·Current Pharmaceutical Design·Rudi VennekensBernd Nilius
Feb 8, 2008·American Journal of Physiology. Renal Physiology·Rajeev RohatgiLisa M Satlin
Aug 8, 2008·American Journal of Physiology. Renal Physiology·Guillermo B Silva, J L Garvin
Aug 13, 2008·The Journal of Cell Biology·Michael KöttgenGerd Walz
Jun 18, 2009·The Journal of Biological Chemistry·Tsutomu MochizukiMakoto Tominaga
Sep 10, 2009·Biochemical and Biophysical Research Communications·Fabien VincentMatthew A J Duncton
Dec 8, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Suelhem A MendozaDavid X Zhang
Aug 20, 2010·American Journal of Physiology. Renal Physiology·Pablo D CabralJ L Garvin
Feb 25, 2011·American Journal of Physiology. Renal Physiology·Pablo D Cabral, J L Garvin
Apr 12, 2012·American Journal of Physiology. Cell Physiology·Mohammad ShahidullahNicholas A Delamere
Apr 13, 2012·American Journal of Physiology. Renal Physiology·Pablo D CabralJ L Garvin
Oct 31, 2012·Journal of Cardiovascular Pharmacology·Jessica A FilosaGeraldine Rath
Jun 27, 2014·American Journal of Physiology. Renal Physiology·Pablo D Cabral, J L Garvin

Citations

Dec 29, 2016·Acta Physiologica·Lajos MarkóMaik Gollasch
Apr 20, 2018·American Journal of Physiology. Renal Physiology·Fara SaezJ L Garvin
Apr 9, 2017·Physiological Genomics·Lesley A GrahamNicholas R Ferreri
Sep 26, 2017·British Journal of Pharmacology·Lídia AmbrusBalázs István Tóth
Oct 26, 2018·Physiological Reviews·Agustin Gonzalez-VicenteJ L Garvin
May 25, 2016·Acta Physiologica·R Mrowka, S Reuter

Related Concepts

Trpv4 protein, rat
Metazoa
Calcium
Dose-Response Relationship, Drug
Structure of Ascending Limb of Henle's Loop
Water-Electrolyte Balance
Ion Channel Gating
Rats, Holtzman
TRPV Cation Channels
Rats, Laboratory

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

The Tendon Seed Network

Tendons are rich in the extracellular matrix and are abundant throughout the body providing essential roles including structure and mobility. The transcriptome of tendons is being compiled to understand the micro-anatomical functioning of tendons. Discover the latest research pertaining to the Tendon Seed Network here.

Myocardial Stunning

Myocardial stunning is a mechanical dysfunction that persists after reperfusion of previously ischemic tissue in the absence of irreversible damage including myocardial necrosis. Here is the latest research.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Incretins

Incretins are metabolic hormones that stimulate a decrease in glucose levels in the blood and they have been implicated in glycemic regulation in the remission phase of type 1 diabetes. Here is the latest research.

Chromatin Regulation and Circadian Clocks

The circadian clock plays an important role in regulating transcriptional dynamics through changes in chromatin folding and remodelling. Discover the latest research on Chromatin Regulation and Circadian Clocks here.

Long COVID-19

“Long Covid-19” describes illness in patients who are reporting long-lasting effects of the SARS-CoV-19 infection, often long after they have recovered from acute Covid-19. Ongoing health issues often reported include low exercise tolerance and breathing difficulties, chronic tiredness, and mental health problems such as post-traumatic stress disorder and depression. This feed follows the latest research into Long Covid.

Spatio-Temporal Regulation of DNA Repair

DNA repair is a complex process regulated by several different classes of enzymes, including ligases, endonucleases, and polymerases. This feed focuses on the spatial and temporal regulation that accompanies DNA damage signaling and repair enzymes and processes.

Related Papers

American Journal of Physiology. Renal Physiology
Pablo D CabralJ L Garvin
American Journal of Physiology. Renal Physiology
Pablo D CabralJ L Garvin
American Journal of Physiology. Renal Physiology
Nancy J Hong, J L Garvin
© 2021 Meta ULC. All rights reserved