مورد إلكتروني
Dehydroepiandrosterone Sulfate (DHEAS) Is an Endogenous Kv7 Channel Modulator That Reduces Kv7/M-Current Suppression and Inflammatory Pain.
| العنوان: | Dehydroepiandrosterone Sulfate (DHEAS) Is an Endogenous Kv7 Channel Modulator That Reduces Kv7/M-Current Suppression and Inflammatory Pain. |
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| المؤلفون: | Alhassen, Lamees |
| المصدر: | Journal of Neuroscience; vol 43, iss 43 |
| بيانات النشر: | eScholarship, University of California 2023-10-25 |
| تفاصيل مُضافة: | Alhassen, Lamees Alhassen, Wedad Wong, Cindy Sun, Yuxuan Xia, Zelin Civelli, Olivier Hoshi, Naoto |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Neuronal Kv7 voltage-gated potassium channels generate the M-current and regulate neuronal excitability. Here, we report that dehydroepiandrosterone sulfate (DHEAS) is an endogenous Kv7 channel modulator that attenuates Gq-coupled receptor-induced M-current suppression. DHEAS reduced muscarinic agonist-induced Kv7-current suppression of Kv7.1, Kv7.2, Kv7.4, or Kv7.5 homomeric currents and endogenous M-currents in rat sympathetic ganglion neurons. However, DHEAS per se did not alter the voltage dependence of these Kv7 homomeric channels or the m1 receptor-induced activation of phospholipase C or protein kinase C. DHEAS-treated Kv7.2 homomeric currents became resistant to depletion of phosphatidylinositol 4,5-bisphosphate (PIP2) induced by voltage-activated phosphatase, Ci-VSP or eVSP. Our computational models predicted a novel binding site for DHEAS in the cytoplasmic domain of Kv7 subunits. A single-point mutation of the predicted key histidine into cysteine in the rat Kv7.2 subunit, rKv7.2(H558C), resulted in a loss of effects of DHEAS on muscarinic Kv7 current suppression. Furthermore, in vivo administration of DHEAS in mice of both sexes reduced late phase pain responses in the formalin paw test. However, it did not have effects on early phase responses in the formalin paw test or responses in the hot plate test. Coadministration of a selective Kv7 inhibitor, XE991, and DHEAS eliminated analgesic effects of DHEAS in late phase responses in the formalin paw test. Collectively, these results suggest that DHEAS attenuates M-current suppression by stabilizing PIP2-Kv7 subunit interaction and can mitigate inflammatory pain.SIGNIFICANCE STATEMENT M-current suppression induced by stimulation of Gq-coupled receptors is a form of Kv7 current modulation that can reversibly increase neuronal excitability. This study demonstrates that DHEAS, an endogenous steroid hormone, is a novel Kv7 channel modulator that can attenuate M-current suppression without affecting basal Kv7 ch |
| مصطلحات الفهرس: | Kv7, analgesic, pain, steroid hormone, voltage-gated potassium channels, Male, Female, Mice, Rats, Animals, Dehydroepiandrosterone Sulfate, KCNQ2 Potassium Channel, Muscarinic Agonists, Pain, Formaldehyde, KCNQ3 Potassium Channel, article |
| URL: | |
| الإتاحة: | Open access content. Open access content public |
| ملاحظة: | application/pdf Journal of Neuroscience vol 43, iss 43 |
| أرقام أخرى: | CDLER oai:escholarship.org:ark:/13030/qt3695j4q2 qt3695j4q2 https://escholarship.org/uc/item/3695j4q2Test https://escholarship.orgTest/ 1410326612 |
| المصدر المساهم: | UC MASS DIGITIZATION From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1410326612 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |