Acid-Sensing Ion Channels
| العنوان: | Acid-Sensing Ion Channels |
|---|---|
| المؤلفون: | John A. Wemmie, Frank M. Faraci, Subhash C. Gupta, Cynthia M. Lynch, Rong Fan, Rebecca J. Taugher |
| المصدر: | Circ Res |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, Physiology, Mice, Transgenic, Vasodilation, Pharmacology, Nitric Oxide, Article, Microcirculation, Nitric oxide, Hypercapnia, Mice, chemistry.chemical_compound, medicine, Animals, Acid-sensing ion channel, Acidosis, Mice, Knockout, Chemistry, Neurodegeneration, Carbon Dioxide, medicine.disease, Acid Sensing Ion Channels, Mice, Inbred C57BL, Cerebral blood flow, Cerebrovascular Circulation, medicine.symptom, Cardiology and Cardiovascular Medicine |
| الوصف: | Rationale: Precise regulation of cerebral blood flow is critical for normal brain function. Insufficient cerebral blood flow contributes to brain dysfunction and neurodegeneration. Carbon dioxide (CO 2 ), via effects on local acidosis, is one of the most potent regulators of cerebral blood flow. Although a role for nitric oxide in intermediate signaling has been implicated, mechanisms that initiate CO 2 -induced vasodilation remain unclear. Objective: Acid-sensing ion channel-1A (ASIC1A) is a proton-gated cation channel that is activated by extracellular acidosis. Based on work that implicated ASIC1A in the amygdala and bed nucleus of the stria terminalis in CO 2 -evoked and acid-evoked behaviors, we hypothesized that ASIC1A might also mediate microvascular responses to CO 2 . Methods and Results: To test this hypothesis, we genetically and pharmacologically manipulated ASIC1A and assessed effects on CO 2 -induced dilation of cerebral arterioles in vivo. Effects of inhalation of 5% or 10% CO 2 on arteriolar diameter were greatly attenuated in mice with global deficiency in ASIC1A ( Asic1a −/− ) or by local treatment with the ASIC inhibitor, psalmotoxin. Vasodilator effects of acetylcholine, which acts via endothelial nitric oxide synthase were unaffected, suggesting a nonvascular source of nitric oxide may be key for CO 2 responses. Thus, we tested whether neurons may be the cell type through which ASIC1A influences microvessels. Using mice in which Asic1a was specifically disrupted in neurons, we found effects of CO 2 on arteriolar diameter were also attenuated. Conclusions: Together, these data are consistent with a model wherein activation of ASIC1A, particularly in neurons, is critical for CO 2 -induced nitric oxide production and vasodilation. With these findings, ASIC1A emerges as major regulator of microvascular tone. |
| تدمد: | 1524-4571 0009-7330 |
| DOI: | 10.1161/circresaha.119.315024 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::25ead7f5083b6c895cdad109c8f3ba65 https://doi.org/10.1161/circresaha.119.315024 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....25ead7f5083b6c895cdad109c8f3ba65 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244571 00097330 |
|---|---|
| DOI: | 10.1161/circresaha.119.315024 |