Blockade of TRPV channels by intracellular spermine.
Grigory MaksaevPeng YuanColin G NicholsPublished in: The Journal of general physiology (2023)
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.
Keyphrases
- neuropathic pain
- immune response
- chronic pain
- spinal cord
- endothelial cells
- spinal cord injury
- pain management
- oxidative stress
- blood brain barrier
- single cell
- reactive oxygen species
- toll like receptor
- blood pressure
- transcription factor
- anti inflammatory
- body composition
- induced pluripotent stem cells
- atopic dermatitis
- genome wide identification