VNUT and VMAT2 segregate within sympathetic varicosities and localize near preferred Cav2 isoforms in the rat tail artery
| العنوان: | VNUT and VMAT2 segregate within sympathetic varicosities and localize near preferred Cav2 isoforms in the rat tail artery |
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| المؤلفون: | Cynthia Gershome, BaRun Kim, Damon Poburko, Nickolas Saraev, Jagdeep Singh Walia, Somayeh Mojarad Kalkhoran, Sarah Heather Jane Chow |
| المصدر: | American Journal of Physiology-Heart and Circulatory Physiology. 316:H89-H105 |
| بيانات النشر: | American Physiological Society, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Gene isoform, Sympathetic Nervous System, Physiology, Presynaptic Terminals, 030204 cardiovascular system & hematology, Immunofluorescence, Vesicular monoamine transporter 2, Neuroeffector junction, Rats, Sprague-Dawley, Norepinephrine, 03 medical and health sciences, Adenosine Triphosphate, Calcium Channels, N-Type, 0302 clinical medicine, Physiology (medical), medicine, Fluorescence microscope, Animals, Protein Isoforms, Rat tail artery, medicine.diagnostic_test, biology, Chemistry, Arteries, Nucleotide Translocase, Rats, Cell biology, 030104 developmental biology, Vasoconstriction, Vesicular Monoamine Transport Proteins, Nucleotide Transport Proteins, biology.protein, Cardiology and Cardiovascular Medicine, medicine.drug |
| الوصف: | ATP and norepinephrine (NE) are coreleased from peripheral sympathetic nerve terminals. Whether they are stored in the same vesicles has been debated for decades. Preferential dependence of NE or ATP release on Ca2+ influx through specific voltage-gated Ca2+ channel (Cav2) isoforms suggests that NE and ATP are stored in separate vesicle pools, but simultaneous imaging of NE and ATP containing vesicles within single varicosities has not been reported. We conducted an immunohistochemical study of vesicular monoamine transporter 2 (VMAT2/SLC18A2) and vesicular nucleotide translocase (VNUT/SLC17A9) as markers of vesicles containing NE and ATP in sympathetic nerves of the rat tail artery. A large fraction of varicosities exhibited neighboring, rather than overlapping, VNUT and VMAT2 fluorescent puncta. VMAT2, but not VNUT, colocalized with synaptotagmin 1. Cav2.1, Cav2.2, and Cav2.3 are expressed in nerves in the tunica adventitia. VMAT2 preferentially localized adjacent to Cav2.2 and Cav2.3 rather than Cav2.1. VNUT preferentially localized adjacent to Cav2.3 > Cav2.2 >> Cav2.1. With the use of wire myography, inhibition of field-stimulated vasoconstriction with the Cav2.3 blocker SNX-482 (0.25 µM) mimicked the effects of the P2X inhibitor suramin (100 µM) rather than the α-adrenergic inhibitor phentolamine (10 µM). Variable sensitivity to SNX-482 and suramin between animals closely correlated with Cav2.3 staining. We concluded that a majority of ATP and NE stores localize to separate vesicle pools that use different synaptotagmin isoforms and that localize near different Cav2 isoforms to mediate vesicle release. Cav2.3 appears to play a previously unrecognized role in mediating ATP release in the rat tail artery. NEW & NOTEWORTHY Immunofluorescence imaging of vesicular nucleotide translocase and vesicular monoamine transporter 2 in rat tail arteries revealed that ATP and norepinephrine, classical cotransmitters, localize to well-segregated vesicle pools. Furthermore, vesicular nucleotide translocase and vesicular monoamine transporter 2 exhibit preferential localization with specific Cav2 isoforms. These novel observations address long-standing debates regarding the mechanism(s) of sympathetic neurotransmitter corelease. |
| تدمد: | 1522-1539 0363-6135 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f465d80d043451d258f2189197eef725Test https://doi.org/10.1152/ajpheart.00560.2018Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f465d80d043451d258f2189197eef725 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221539 03636135 |
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