Kv1.1 channels act as mechanical brake in the senses of touch and pain
| Autor: | Jizhe Hao, Florian Lesage, Catharina Lavebratt, Patrick Delmas, Françoise Padilla, Jacques Noël, Mathieu Dandonneau |
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| Přispěvatelé: | Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA) |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
MESH: Signal Transduction
Patch-Clamp Techniques Dominant negative Membrane Potentials Mice Potassium Channels Calcium-Activated 0302 clinical medicine Nerve Fibers MESH: Sensory Receptor Cells Brake MESH: Animals MESH: Nociceptors 0303 health sciences Mice Inbred BALB C Mice Inbred C3H KCNQ Potassium Channels Chemistry General Neuroscience MESH: Pain Threshold Nociceptors Depolarization MESH: Kv1.1 Potassium Channel MESH: Touch Immunohistochemistry Hyperalgesia MESH: Potassium Channels Calcium-Activated Data Interpretation Statistical Sensory Thresholds Excitatory postsynaptic potential Mechanosensitive channels MESH: Pain Mechanoreceptors Signal Transduction Pain Threshold Sensory Receptor Cells Neuroscience(all) MESH: Mice Inbred BALB C Pain MESH: Ether-A-Go-Go Potassium Channels Mechanical Allodynia Open probability 03 medical and health sciences MESH: Mice Inbred C57BL Physical Stimulation MESH: Patch-Clamp Techniques Animals MESH: Membrane Potentials MESH: Physical Stimulation [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] MESH: Mice Inbred C3H MESH: Mice MESH: Nerve Fibers 030304 developmental biology Communication business.industry MESH: Mechanoreceptors MESH: Immunohistochemistry MESH: Hyperalgesia Ether-A-Go-Go Potassium Channels Mice Inbred C57BL nervous system Touch Biophysics MESH: KCNQ Potassium Channels Heat hyperalgesia MESH: Sensory Thresholds business Kv1.1 Potassium Channel MESH: Data Interpretation Statistical 030217 neurology & neurosurgery |
| Zdroj: | Neuron Neuron, Elsevier, 2013, 77 (5), pp.899-914. ⟨10.1016/j.neuron.2012.12.035⟩ Neuron, 2013, 77 (5), pp.899-914. ⟨10.1016/j.neuron.2012.12.035⟩ |
| ISSN: | 0896-6273 |
| Popis: | International audience; Molecular determinants of threshold sensitivity of mammalian mechanoreceptors are unknown. Here, we identify a mechanosensitive (MS) K(+) current (IKmech) that governs mechanical threshold and adaptation of distinct populations of mechanoreceptors. Toxin profiling and transgenic mouse studies indicate that IKmech is carried by Kv1.1-Kv1.2 heteromers. Mechanosensitivity is attributed to Kv1.1 subunits, through facilitation of voltage-dependent open probability. IKmech is expressed in high-threshold C-mechano-nociceptors (C-HTMRs) and Aβ-mechanoreceptors, but not in low-threshold C-mechanoreceptors. IKmech opposes depolarization induced by slow/ultraslow MS cation currents in C-HTMRs, thereby shifting mechanical threshold for firing to higher values. However, due to kinetics mismatch with rapidly-adapting MS cation currents, IKmech tunes firing adaptation but not mechanical threshold in Aβ-mechanoreceptors. Expression of Kv1.1 dominant negative or inhibition of Kv1.1/IKmech caused severe mechanical allodynia but not heat hyperalgesia. By balancing the activity of excitatory mechanotransducers, Kv1.1 acts as a mechanosensitive brake that regulates mechanical sensitivity of fibers associated with mechanical perception. |
| Databáze: | OpenAIRE |
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