The Vanilloid thermoTRP (TRPV1–4) subfamily of TRP channels are involved in thermoregulation, osmoregulation, itch and pain perception, (neuro)inflammation and immune response, and tight control of channel activity is required for perception of noxious stimuli and pain. Here we report voltage-dependent modulation of each of human TRPV1, 3, and 4 by the endogenous intracellular polyamine spermine. As in inward rectifier K channels, currents are blocked in a strongly voltage-dependent manner, but, as in cyclic nucleotide-gated channels, the blockade is substantially reduced at more positive voltages, with maximal blockade in the vicinity of zero voltage. A kinetic model of inhibition suggests two independent spermine binding sites with different affinities as well as different degrees of polyamine permeability in TRPV1, 3, and 4. Given that block and relief occur over the physiological voltage range of action potentials, voltage-dependent polyamine block may be a potent modulator of TRPV-dependent excitability in multiple cell types.
Skip Nav Destination
Article navigation
1 May 2023
Article|
March 13 2023
Blockade of TRPV channels by intracellular spermine
Grigory Maksaev
,
1
Department of Cell Biology and Physiology, Center for Investigation of Membrane Excitability Diseases, Washington University School of Medicine
, St. Louis, MO, USA
Correspondence to Grigory Maksaev: gmaksaev@wustl.edu
Search for other works by this author on:
Peng Yuan,
Peng Yuan
1
Department of Cell Biology and Physiology, Center for Investigation of Membrane Excitability Diseases, Washington University School of Medicine
, St. Louis, MO, USA
Search for other works by this author on:
Colin G. Nichols
Colin G. Nichols
1
Department of Cell Biology and Physiology, Center for Investigation of Membrane Excitability Diseases, Washington University School of Medicine
, St. Louis, MO, USA
Search for other works by this author on:
1
Department of Cell Biology and Physiology, Center for Investigation of Membrane Excitability Diseases, Washington University School of Medicine
, St. Louis, MO, USA
Peng Yuan
1
Department of Cell Biology and Physiology, Center for Investigation of Membrane Excitability Diseases, Washington University School of Medicine
, St. Louis, MO, USA
Colin G. Nichols
1
Department of Cell Biology and Physiology, Center for Investigation of Membrane Excitability Diseases, Washington University School of Medicine
, St. Louis, MO, USA
Correspondence to Grigory Maksaev: gmaksaev@wustl.edu
P. Yuan’s current affiliation is Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Received:
September 29 2022
Revision Received:
January 20 2023
Accepted:
February 28 2023
Online ISSN: 1540-7748
Print ISSN: 0022-1295
Funding
Funder(s):
National Institutes of Health
- Award Id(s): R01 NS099341
© 2023 Maksaev et al.
2023
Maksaev et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Gen Physiol (2023) 155 (5): e202213273.
Article history
Received:
September 29 2022
Revision Received:
January 20 2023
Accepted:
February 28 2023
Citation
Grigory Maksaev, Peng Yuan, Colin G. Nichols; Blockade of TRPV channels by intracellular spermine. J Gen Physiol 1 May 2023; 155 (5): e202213273. doi: https://doi.org/10.1085/jgp.202213273
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your Institution
643
Views
Suggested Content
A cooperative knock-on mechanism underpins Ca2+-selective cation permeation in TRPV channels
J Gen Physiol (March,2023)
Thermosensitive TRPV Channel Subunits Coassemble into Heteromeric Channels with Intermediate Conductance and Gating Properties
J Gen Physiol (February,2007)
A combined coarse-grained and all-atom simulation of TRPV1 channel gating and heat activation
J Gen Physiol (April,2015)
Email alerts
Advertisement