Opioid-Mediated Modulation of Acid-Sensing Ion Channel Currents in Adult Rat Sensory Neurons

Molecular Pharmacology
Malgorzata Zaremba, Victor Ruiz-Velasco

Abstract

Muscle ischemia, associated with peripheral artery disease (PAD), leads to the release of proinflammatory mediators that decrease extracellular pH and trigger the activation of proton-activated acid-sensing ion channels (ASIC). Claudication pain, linked with low blood flow, can be partially relieved by endogenous opioid peptide release. However, we previously reported that sustained ASIC currents in dorsal root ganglion (DRG) neurons were enhanced by naturally occurring endomorphin-1 and -2 opioid peptides, indicating a role of opioid involvement in hyperalgesia. The present study examined whether clinically employed synthetic (fentanyl, remifentanil) and the semisynthetic opioid (oxycodone) would also potentiate sustained ASIC currents, which arise from ASIC3 channel isoforms. Here, we show that exposure of each opioid to DRG neurons resulted in potentiation of the sustained ASIC currents. On the other hand, the potentiation was not observed in DRG neurons from ASIC3 knockout rats. Further, the enhancement of the ASIC currents was resistant to pertussis toxin treatment, suggesting that Gαi/Gαo G-proteins are not involved. Additionally, the potentiation of sustained ASIC currents was greater in DRG neurons isolated from rats wi...Continue Reading

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Citations

Apr 18, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Joyce S KimMarc P Kaufman
Aug 28, 2019·Journal of Comparative Physiology. A, Neuroethology, Sensory, Neural, and Behavioral Physiology·Ziya CakirRamazan Bal
Jul 28, 2019·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Joyce S KimMarc P Kaufman
Apr 9, 2021·Peptides·Richard J Bodnar

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