Molecular mechanisms of lipoic acid modulation of T-type calcium channels in pain pathway
| Autor: | Michael T. Nelson, Peihan Orestes, Woo Yong Lee, Iuliia Vitko, Ajit K. Naik, Slobodan M. Todorovic, Vesna Jevtovic-Todorovic, Janelle R. Latham, Edward Perez-Reyes |
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| Rok vydání: | 2009 |
| Předmět: |
Pain Threshold
Sensory Receptor Cells chemistry.chemical_element Pain Calcium Pharmacology Article Cell Line chemistry.chemical_compound Calcium Channels T-Type Mice In vivo Ganglia Spinal Animals Humans Amino Acid Sequence Cells Cultured Mice Knockout Analgesics Thioctic Acid General Neuroscience HEK 293 cells T-type calcium channel Nociceptors Rats Lipoic acid Nociception chemistry Biochemistry Nociceptor lipids (amino acids peptides and proteins) Oxidation-Reduction |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 29(30) |
| ISSN: | 1529-2401 |
| Popis: | α-Lipoic acid (1,2-dithiolane-3-pentanoic acid; lipoic acid) is an endogenous compound used to treat pain disorders in humans, but its mechanisms of analgesic action are not well understood. Here, we show that lipoic acid selectively inhibited native CaV3.2 T-type calcium currents (T-currents) and diminished T-channel-dependent cellular excitability in acutely isolated rat sensory neurons. Lipoic acid locally injected into peripheral receptive fields of pain-sensing sensory neurons (nociceptors)in vivodecreased sensitivity to noxious thermal and mechanical stimuli in wild-type but not CaV3.2 knock-out mice. Ensuing molecular studies demonstrated that lipoic acid inhibited recombinant CaV3.2 channels heterologously expressed in human embryonic kidney 293 cells by oxidating specific thiol residues on the cytoplasmic face of the channel. This study provides the first mechanistic demonstration of a nociceptive ion channel modulation that may contribute to the documented analgesic properties of lipoic acidin vivo. |
| Databáze: | OpenAIRE |
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