RyR2 modulates a Ca2+-activated K+ current in mouse cardiac myocytes.
RyR2 modulates a Ca2+-activated K+ current in mouse cardiac myocytes.
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DOI：
10.1371/journal.pone.0094905
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zhang Q
中科院分区：
文献类型：
--
作者：
Mu YH;Zhao WC;Duan P;Chen Y;Zhao WD;Wang Q;Tu HY;Zhang Q
在心肌细胞中，通过电压依赖性Ca 2+通道（VDCCs）的Ca 2+进入结合并激活RyR 2通道，导致随后从肌浆网（SR）释放Ca 2+和心脏收缩。先前的研究已经证明了小鼠心肌中小电导Ca 2+激活的K+通道（SK通道）与VDCCs的分子偶联。关于RyRs敏感的Ca 2+释放在心肌SK通道中的作用知之甚少。本研究采用全细胞膜片钳技术，观察到RyR 2抑制剂ryanodine或与肌浆网钙ATP酶抑制剂thapsigargin合用，均能显著降低C57 B/L小鼠心房肌细胞钙激活钾电流（IK，Ca）。（分别为p<0.05，p<0.01）。咖啡因激活RyR 2可使心肌细胞IK、Ca增加（分别为p<0.05、p<0.01）。我们使用全细胞膜片钳技术和共聚焦成像进一步分析了RyR 2敲低对离体成年小鼠心肌细胞IK、Ca和Ca 2+的影响。用慢病毒介导的小发夹干扰RNA（shRNA）转导的小鼠心房细胞中RyR 2敲低显示IK、Ca（p<0.05）和[Ca 2 +]i荧光强度显着降低（p<0.01）。通过免疫共沉淀试验在天然心脏组织中鉴定了SK2和RyR 2的免疫沉淀复合物。我们的研究结果表明，RyR 2介导的Ca 2+释放是负责在心肌细胞中的SK通道的激活和调制。
In cardiomyocytes, Ca2+ entry through voltage-dependent Ca2+ channels (VDCCs) binds to and activates RyR2 channels, resulting in subsequent Ca2+ release from the sarcoplasmic reticulum (SR) and cardiac contraction. Previous research has documented the molecular coupling of small-conductance Ca2+-activated K+ channels (SK channels) to VDCCs in mouse cardiac muscle. Little is known regarding the role of RyRs-sensitive Ca2+ release in the SK channels in cardiac muscle. In this study, using whole-cell patch clamp techniques, we observed that a Ca2+-activated K+ current (IK,Ca) recorded from isolated adult C57B/L mouse atrial myocytes was significantly decreased by ryanodine, an inhibitor of ryanodine receptor type 2 (RyR2), or by the co-application of ryanodine and thapsigargin, an inhibitor of the sarcoplasmic reticulum calcium ATPase (SERCA) (p<0.05, p<0.01, respectively). The activation of RyR2 by caffeine increased the IK,Ca in the cardiac cells (p<0.05, p<0.01, respectively). We further analyzed the effect of RyR2 knockdown on IK,Ca and Ca2+ in isolated adult mouse cardiomyocytes using a whole-cell patch clamp technique and confocal imaging. RyR2 knockdown in mouse atrial cells transduced with lentivirus-mediated small hairpin interference RNA (shRNA) exhibited a significant decrease in IK,Ca (p<0.05) and [Ca2+]i fluorescence intensity (p<0.01). An immunoprecipitated complex of SK2 and RyR2 was identified in native cardiac tissue by co-immunoprecipitation assays. Our findings indicate that RyR2-mediated Ca2+ release is responsible for the activation and modulation of SK channels in cardiac myocytes.
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影响因子：
4.8
作者：
Xu, YF;Tuteja, D;Chiamvimonvat, N
通讯作者：
Chiamvimonvat, N
影响因子：
4.8
作者：
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通讯作者：
Anderson, AE
影响因子：
56.9
作者：
CANNELL, MB;CHENG, H;LEDERER, WJ
通讯作者：
LEDERER, WJ
影响因子：
20.1
作者：
Lu, Ling;Zhang, Qian;Chiamvimonvat, Nipavan
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Chiamvimonvat, Nipavan
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影响因子：
5.5
作者：
Li, Ning;Timofeyev, Valeriy;Chiamvimonvat, Nipavan
通讯作者：
Chiamvimonvat, Nipavan