Heat-evoked Activation of TRPV4 Channels in a HEK293 Cell Expression System and in Native Mouse Aorta Endothelial Cells*

By Hiroyuki Watanabe, J. Vriens, S. Suh, C. Benham, G. Droogmans, B. Nilius. Journal of Biological Chemistry, 2002

662 citations recorded by the source corpus.

We have compared activation by heat of TRPV4 channels, heterogeneously expressed in HEK293 cells, and endogenous channels in mouse aorta endothelium (MAEC). Increasing the temperature above 25 °C activated currents and increased [Ca2+] i in HEK293 cells transfected with TRPV4 and in MAEC. When compared with activation of TRPV4 currents by the selective ligand 4αPDD (α-phorbol 12,13-didecanoate), heat-activated currents in both systems showed the typical biophysical properties of currents through TRPV4, including their single channel conductance. Deletion of the three N-terminal ankyrin binding domains of TRPV4 abolished current activation cells by heat in HEK293. In inside-out patches, TRPV4 could not be activated by heat but still responded to the ligand 4αPDD. In MAEC, the same channel is activated under identical conditions as in the HEK expression system. Our data indicate that TRPV4 is a functional temperature-sensing channel in native endothelium, that is likely involved in temperature-dependent Ca2+ signaling. The failure to activate TRPV4 channels by heat in inside-out patches, which responded to 4αPDD, may indicate that heat activation depends on the presence of an endogenous ligand, which is missing in inside-out patches.

Subfields: Cellular and Molecular Neuroscience, Physiology, Sensory Systems

View Paper: https://www.semanticscholar.org/paper/306812953b3c0e68c72861ab1f2f4f072d37e717

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Citations in the corpus

TRP Channels (2012, neutral): “Pore properties TRPV4 is a moderate Ca2+ selective cation channel with a PCa2+/PNa+ = 6-10 (390, 452, 470).”
An introduction to TRP channels. (2006, background): “7 agonist (114) I HEK resiniferatoxin TRPV1 84pM-39nM ~2 agonist (70, 96, 102, 115, 116) B, I, Ca X,CHO”
The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels (2004, background): “Four TRP channels belonging to the TRPV subfamily are activated by heating, with characteristic activation temperatures ranging from warm temperatures (> 25 °C for TRPV4; >31 °C for TRPV3”
Trp ion channels and temperature sensation. (2006, background): “TRPV4, originally identified as an osmosensory ion channel, is also activated by warm temperatures (25◦C–34◦C) (Guler et al. 2002, Liedtke et al. 2000, Strotmann et al. 2000, Watanabe et al. 2002).”
The TRP Superfamily of Cation Channels (2005, background): “J. Vriens, H. Watanabe, A. Janssens, G. Droogmans, T. Voets, B. Nilius, Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4.”