{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:24:32Z","timestamp":1787027072187,"version":"build-2736575974"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T00:00:00Z","timestamp":1646956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>\n                    In mesenteric arteries (MAs), aldosterone (ALDO) binds to the endogenous mineralocorticoid receptor (MR) and increases the expression of the voltage-gated L-type Ca\n                    <jats:sub>v<\/jats:sub>\n                    1.2 channel, an essential ion channel for vascular contraction, sarcoplasmic reticulum (SR) Ca\n                    <jats:sup>2+<\/jats:sup>\n                    store refilling, and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    spark generation. In mesenteric artery smooth muscle cells (MASMCs), Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx through Ca\n                    <jats:sub>v<\/jats:sub>\n                    1.2 is the indirect mechanism for triggering Ca\n                    <jats:sup>2+<\/jats:sup>\n                    sparks. This process is facilitated by plasma membrane-sarcoplasmic reticulum (PM-SR) nanojunctions that drive Ca\n                    <jats:sup>2+<\/jats:sup>\n                    from the extracellular space into the SR via Sarco\/Endoplasmic Reticulum Ca\n                    <jats:sup>2+<\/jats:sup>\n                    (SERCA) pump. Ca\n                    <jats:sup>2+<\/jats:sup>\n                    sparks produced by clusters of Ryanodine receptors (RyRs) at PM-SR nanodomains, decrease contractility by activating large-conductance Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -activated K\n                    <jats:sup>+<\/jats:sup>\n                    channels (BK\n                    <jats:sub>Ca<\/jats:sub>\n                    channels), which generate spontaneous transient outward currents (STOCs). Altogether, Ca\n                    <jats:sub>v<\/jats:sub>\n                    1.2, SERCA pump, RyRs, and BK\n                    <jats:sub>Ca<\/jats:sub>\n                    channels work as a functional unit at the PM-SR nanodomain, regulating intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and vascular function. However, the effect of the ALDO\/MR signaling pathway on this functional unit has not been completely explored. Our results show that short-term exposure to ALDO (10 nM, 24 h) increased the expression of Ca\n                    <jats:sub>v<\/jats:sub>\n                    1.2 in rat MAs. The depolarization-induced Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry increased SR Ca\n                    <jats:sup>2+<\/jats:sup>\n                    load, and the frequencies of both Ca\n                    <jats:sup>2+<\/jats:sup>\n                    sparks and STOCs, while [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>cyt<\/jats:sub>\n                    and vasoconstriction remained unaltered in Aldo-treated MAs. ALDO treatment significantly increased the mRNA and protein expression levels of the SERCA pump, which counterbalanced the augmented Ca\n                    <jats:sub>v<\/jats:sub>\n                    1.2-mediated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx at the PM-SR nanodomain, increasing SR Ca\n                    <jats:sup>2+<\/jats:sup>\n                    content, Ca\n                    <jats:sup>2+<\/jats:sup>\n                    spark and STOC frequencies, and opposing to hyperpolarization-induced vasoconstriction while enhancing Acetylcholine-mediated vasorelaxation. This work provides novel evidence for short-term ALDO-induced upregulation of the functional unit comprising Ca\n                    <jats:sub>v<\/jats:sub>\n                    1.2, SERCA2 pump, RyRs, and BK\n                    <jats:sub>Ca<\/jats:sub>\n                    channels; in which the SERCA pump buffers ALDO-induced upregulation of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry at the superficial SR-PM nanodomain of MASMCs, preventing ALDO-triggered depolarization-induced vasoconstriction and enhancing vasodilation. Pathological conditions that lead to SERCA pump downregulation, for instance, chronic exposure to ALDO, might favor the development of ALDO\/MR-mediated augmented vasoconstriction of mesenteric arteries.\n                  <\/jats:p>","DOI":"10.3389\/fphys.2022.834220","type":"journal-article","created":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T16:54:29Z","timestamp":1647017669000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Aldosterone-Induced Sarco\/Endoplasmic Reticulum Ca2+ Pump Upregulation Counterbalances Cav1.2-Mediated Ca2+ Influx in Mesenteric Arteries"],"prefix":"10.3389","volume":"13","author":[{"given":"Rogelio","family":"Salazar-Enciso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agust\u00edn","family":"Guerrero-Hern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana M.","family":"G\u00f3mez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Benitah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang\u00e9lica","family":"Rueda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"H58","DOI":"10.1152\/AJPHEART.00476.2012","article-title":"Identification of L- and T-type Ca2+ channels in rat cerebral arteries: role in myogenic tone development.","volume":"304","author":"Abd El-Rahman","year":"2013","journal-title":"Am. 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