{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:49:26Z","timestamp":1762102166983,"version":"3.41.0"},"reference-count":44,"publisher":"American Physiological Society","issue":"1","funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23390020","26293021","15H01408","25136717"],"award-info":[{"award-number":["23390020","26293021","15H01408","25136717"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2018,7,1]]},"abstract":"<jats:p>Physiological functions of type 3 ryanodine receptors (RyR3) in smooth muscle (SM) tissues are not well understood, in spite of their wide expression. However, the short isoform of RyR3 is known to be a dominant-negative variant (DN-RyR3), which may negatively regulate functions of both RyR2 and full-length (FL) RyR3 by forming hetero-tetramers. Here, functional roles of RyR3 in the regulation of Ca<jats:sup>2+<\/jats:sup>signaling in mesenteric artery SM cells (MASMCs) were examined using RyR3 homozygous knockout mice (RyR3<jats:sup>\u2212\/\u2212<\/jats:sup>). Quantitative PCR analyses suggested that the predominant RyR3 subtype in MASMs from wild-type mice (RyR3<jats:sup>+\/+<\/jats:sup>) was DN-RyR3. In single MASMCs freshly isolated from RyR3<jats:sup>\u2212\/\u2212<\/jats:sup>, the EC<jats:sub>50<\/jats:sub>of caffeine to induce Ca<jats:sup>2+<\/jats:sup>release was lower than that in RyR3<jats:sup>+\/+<\/jats:sup>myocytes. The amplitude and frequency of Ca<jats:sup>2+<\/jats:sup>sparks and spontaneous transient outward currents in MASMCs from RyR3<jats:sup>\u2212\/\u2212<\/jats:sup>were all larger than those from RyR3<jats:sup>+\/+<\/jats:sup>. Importantly, mRNA and functional expressions of voltage-dependent Ca<jats:sup>2+<\/jats:sup>channel and large-conductance Ca<jats:sup>2+<\/jats:sup>-activated K<jats:sup>+<\/jats:sup>(BK) channel in MASMCs from RyR3<jats:sup>\u2212\/\u2212<\/jats:sup>were identical to those from RyR3<jats:sup>+\/+<\/jats:sup>. However, in the presence of BK channel inhibitor, paxilline, the pressure rises induced by BayK8644 in MA vascular beds of RyR3<jats:sup>\u2212\/\u2212<\/jats:sup>were significantly larger than in those of RyR3<jats:sup>+\/+<\/jats:sup>. This indicates that the negative feedback effects of BK channel activity on intracellular Ca<jats:sup>2+<\/jats:sup>signaling was enhanced in RyR3<jats:sup>\u2212\/\u2212<\/jats:sup>. Thus, RyR3, and, in fact, mainly DN-RyR3, via a complex with RyR2 suppresses Ca<jats:sup>2+<\/jats:sup>release and indirectly regulated membrane potential by reducing BK channel activity in MASMCs and presumably can affect the regulation of intrinsic vascular tone.<\/jats:p>","DOI":"10.1152\/ajpcell.00006.2018","type":"journal-article","created":{"date-parts":[[2018,3,14]],"date-time":"2018-03-14T20:29:37Z","timestamp":1521059377000},"page":"C1-C9","source":"Crossref","is-referenced-by-count":10,"title":["Negative regulation of cellular Ca<sup>2+<\/sup>mobilization by ryanodine receptor type 3 in mouse mesenteric artery smooth muscle"],"prefix":"10.1152","volume":"315","author":[{"given":"Katsuhito","family":"Matsuki","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 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