| First Author | Matsuki K | Year | 2018 |
| Journal | Am J Physiol Cell Physiol | Volume | 315 |
| Issue | 1 | Pages | C1-C9 |
| PubMed ID | 29537866 | Mgi Jnum | J:263191 |
| Mgi Id | MGI:6188348 | Doi | 10.1152/ajpcell.00006.2018 |
| Citation | Matsuki K, et al. (2018) Negative regulation of cellular Ca(2+) mobilization by ryanodine receptor type 3 in mouse mesenteric artery smooth muscle. Am J Physiol Cell Physiol 315(1):C1-C9 |
| abstractText | 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(2+) signaling in mesenteric artery SM cells (MASMCs) were examined using RyR3 homozygous knockout mice (RyR3(-/-)). Quantitative PCR analyses suggested that the predominant RyR3 subtype in MASMs from wild-type mice (RyR3(+/+)) was DN-RyR3. In single MASMCs freshly isolated from RyR3(-/-), the EC50 of caffeine to induce Ca(2+) release was lower than that in RyR3(+/+) myocytes. The amplitude and frequency of Ca(2+) sparks and spontaneous transient outward currents in MASMCs from RyR3(-/-) were all larger than those from RyR3(+/+). Importantly, mRNA and functional expressions of voltage-dependent Ca(2+) channel and large-conductance Ca(2+)-activated K(+) (BK) channel in MASMCs from RyR3(-/-) were identical to those from RyR3(+/+). However, in the presence of BK channel inhibitor, paxilline, the pressure rises induced by BayK8644 in MA vascular beds of RyR3(-/-) were significantly larger than in those of RyR3(+/+). This indicates that the negative feedback effects of BK channel activity on intracellular Ca(2+) signaling was enhanced in RyR3(-/-). Thus, RyR3, and, in fact, mainly DN-RyR3, via a complex with RyR2 suppresses Ca(2+) release and indirectly regulated membrane potential by reducing BK channel activity in MASMCs and presumably can affect the regulation of intrinsic vascular tone. |
