Transient receptor potential (TRP) channels detect diverse sensory stimuli, including alterations in osmolarity. However, a molecular detector of noxious hypertonic stimuli has not yet been identified. We show here that acute pain-related behavior evoked by elevated ionic strength is abolished in TRP vanilloid subtype 1 (TRPV1)-null mice and inhibited by iodoresiniferatoxin, a potent TRPV1 antagonist. Electrophysiological recordings demonstrate a novel form of ion channel modulation by which extracellular Na+, Mg2+, and Ca2+ ions sensitize and activate the capsaicin receptor, TRPV1. At room temperature, increasing extracellular Mg2+ (from 1 to 5 mM) or Na+ (+50 mM) increased ligand-activated currents up to fourfold, and 10 mM Mg2+ reduced the EC50 for activation by capsaicin from 890 to 450 nM. Moreover, concentrations of divalent cations >10 mM directly gate the receptor. These effects occur via electrostatic interactions with two glutamates (E600 and E648) formerly identified as proton-binding residues. Furthermore, phospholipase C-mediated signaling enhances the effects of cations, and physiological concentrations of cations contribute to the bradykinin-evoked activation of TRPV1 and the sensitization of the receptor to heat...Continue Reading
Facilitation of sympathetic neurotransmission by phosphatidylinositol-4,5-bisphosphate-dependent regulation of KCNQ channels in rat mesenteric arteries
Distinct modulations of human capsaicin receptor by protons and magnesium through different domains.
C-terminal dimerization activates the nociceptive transduction channel transient receptor potential vanilloid 1.
Selective disruption of high sensitivity heat activation but not capsaicin activation of TRPV1 channels by pore turret mutations.
Transient receptor potential vanilloid-1 (TRPV1) is a mediator of lung toxicity for coal fly ash particulate material
The vanilloid receptor TRPV1 is activated and sensitized by local anesthetics in rodent sensory neurons
Intradermal administration of magnesium sulphate and magnesium chloride produces hypesthesia to mechanical but hyperalgesia to heat stimuli in humans.
Transient receptor potential channels encode volatile chemicals sensed by rat trigeminal ganglion neurons
Activation of TRPV1 mediates thymic stromal lymphopoietin release via the Ca2+/NFAT pathway in airway epithelial cells
The role of endogenous molecules in modulating pain through transient receptor potential vanilloid 1 (TRPV1).
Dopamine modulation of transient receptor potential vanilloid type 1 (TRPV1) receptor in dorsal root ganglia neurons
Transient receptor potential V1 regulates activation and modulation of transient receptor potential A1 by Ca2+
Transient receptor potential vanilloid-1 mediates heat-shock-induced matrix metalloproteinase-1 expression in human epidermal keratinocytes
Feedback mechanisms in the regulation of intracellular calcium ([Ca2+]i) in the peripheral nociceptive system: role of TRPV-1 and pain related receptors
Hypertonic saline cough provocation test with salbutamol pre-treatment: evidence for sensorineural dysfunction in asthma
Calcium & Bioenergetics
Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.