Publications by authors named "Ana E Lopez-Romero"

The TMEM16A channel, a member of the TMEM16 protein family comprising chloride (Cl) channels and lipid scramblases, is activated by the free intracellular Ca increments produced by inositol 1,4,5-trisphosphate (IP3)-induced Ca release after GqPCRs or Ca entry through cationic channels. It is a ubiquitous transmembrane protein that participates in multiple physiological functions essential to mammals' lives. TMEM16A structure contains two identical 10-segment monomers joined at their transmembrane segment 10.

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Chloride fluxes through homo-dimeric calcium-activated channels TMEM16A and TMEM16B are critical to blood pressure, gastrointestinal motility, hormone, fluid and electrolyte secretion, pain sensation, sensory transduction, and neuronal and muscle excitability. Their gating depends on the voltage-dependent binding of two intracellular calcium ions to a high-affinity site formed by acidic residues from α-helices 6-8 in each monomer. Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), a low-abundant lipid of the inner leaflet, supports TMEM16A function; it allows TMEM16A to evade the down-regulation induced by calcium, poly-L-lysine, or PI(4,5)P2 5-phosphatase.

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The Transient Receptor Potential Vanilloid 4 (TRPV4) channel has been shown to function in many physiological and pathophysiological processes. Despite abundant information on its importance in physiology, very few endogenous agonists for this channel have been described, and very few underlying mechanisms for its activation have been clarified. TRPV4 is expressed by several types of cells, such as vascular endothelial, and skin and lung epithelial cells, where it plays pivotal roles in their function.

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Numerous essential physiological processes depend on the TMEM16A-mediated Ca2+-activated chloride fluxes. Extensive structure-function studies have helped to elucidate the Ca2+ gating mechanism of TMEM16A, revealing a Ca2+-sensing element close to the anion pore that alters conduction. However, substrate selection and the substrate-gating relationship in TMEM16A remain less explored.

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The widely expressed two-pore homodimeric inward rectifier CLC-2 chloride channel regulates transepithelial chloride transport, extracellular chloride homeostasis, and neuronal excitability. Each pore is independently gated at hyperpolarized voltages by a conserved pore glutamate. Presumably, exiting chloride ions push glutamate outwardly while external protonation stabilizes it.

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Article Synopsis
  • Limited understanding of pruritus (itch) mechanisms in cholestatic liver diseases hampers the development of effective treatments, with lysophosphatidic acid (LPA) previously suggested as a potential mediator.
  • *The study examined the pruritogenic effects of its precursor, lysophosphatidylcholine (LPC), through various experiments involving different animal models and human patient samples, highlighting the role of TRPV4 channels in skin keratinocytes.
  • *Results showed that LPC triggers itch by activating TRPV4 in keratinocytes, leading to the release of miR-146a, which in turn activates TRPV1 sensory neurons; elevated levels of LPC and miR-146a were found in the serum of patients
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Ion channels display conformational changes in response to binding of their agonists and antagonists. The study of the relationships between the structure and the function of these proteins has witnessed considerable advances in the last two decades using a combination of techniques, which include electrophysiology, optical approaches (i.e.

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The transient receptor potential vanilloid 1 (TRPV1) ion channel is mainly found in primary nociceptive afferents whose activity has been linked to pathophysiological conditions including pain, itch and inflammation. Consequently, it is important to identify naturally occurring antagonists of this channel. Here we show that a naturally occurring monounsaturated fatty acid, oleic acid, inhibits TRPV1 activity, and also pain and itch responses in mice by interacting with the vanilloid (capsaicin)-binding pocket and promoting the stabilization of a closed state conformation.

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