Facilitation of cytosolic calcium wave propagation by local calcium uptake into the sarcoplasmic reticulum in cardiac myocytes
Facilitation of cytosolic calcium wave propagation by local calcium uptake into the sarcoplasmic reticulum in cardiac myocytes
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DOI：
10.1113/jphysiol.2012.239434
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发表时间：
2012-12-01
影响因子：
5.5
通讯作者：
Blatter, Lothar A.
中科院分区：
文献类型：
--
作者：
Maxwell, Joshua T.;Blatter, Lothar A.
广泛接受的胞质Ca 2+波传播的范例假设了一种火-扩散-火机制，其中局部Ca 2+诱导的Ca 2+释放（CICR）通过Ryanodine受体（RyR）Ca 2+释放通道从肌浆网（SR）扩散并激活邻近的释放位点，导致传播的Ca 2+波。最近对这种模式的挑战提出了对SR内致敏Ca 2+波的要求，该波先于胞质Ca 2+波并将RyR从腔侧引发至CICR。在这里，我们测试了这一假设的实验与直接同时测量胞浆（[Ca 2 +]i; rhod-2）和SR内（[Ca 2 +]SR; fluo-5 N）钙信号在波传播过程中，在兔心室肌细胞，使用高分辨率荧光共聚焦成像。[Ca 2 +]i在波前的增加之前耗尽的SR在每个点沿着的钙波阵面，而在此潜伏期内的[Ca 2 +]SR的短暂增加被观察到。这种瞬时升高的[Ca ~（2+）]SR可以确定在个别的释放交界处，并依赖于活性的肌内质网Ca ~（2+）-ATP酶（SERCA）。增加SERCA活性（β-肾上腺素能刺激与1 μ m异丙肾上腺素（异丙肾上腺素））的潜伏期缩短，并增加幅度的瞬时升高的[Ca 2 +]SR，而抑制SERCA（3 μ m cyclopiazonic酸）有相反的效果。总之，这些数据提供了实验证据表明，局部钙摄取SERCA进入SR促进细胞溶质钙波的传播通过腔敏化的RyR，并支持一个新的范例的火弥漫摄取火机制的钙波传播心肌细胞。
The widely accepted paradigm for cytosolic Ca2+ wave propagation postulates a fire-diffuse-fire mechanism where local Ca2+-induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR) via ryanodine receptor (RyR) Ca2+ release channels diffuses towards and activates neighbouring release sites, resulting in a propagating Ca2+ wave. A recent challenge to this paradigm proposed the requirement for an intra-SR sensitization Ca2+ wave that precedes the cytosolic Ca2+ wave and primes RyRs from the luminal side to CICR. Here, we tested this hypothesis experimentally with direct simultaneous measurements of cytosolic ([Ca2+]i; rhod-2) and intra-SR ([Ca2+]SR; fluo-5N) calcium signals during wave propagation in rabbit ventricular myocytes, using high resolution fluorescence confocal imaging. The increase in [Ca2+]i at the wave front preceded depletion of the SR at each point along the calcium wave front, while during this latency period a transient increase of [Ca2+]SR was observed. This transient elevation of [Ca2+]SR could be identified at individual release junctions and depended on the activity of the sarco-endoplasmic reticulum Ca2+-ATPase (SERCA). Increased SERCA activity (beta-adrenergic stimulation with 1 mu m isoproterenol (isoprenaline)) decreased the latency period and increased the amplitude of the transient elevation of [Ca2+]SR, whereas inhibition of SERCA (3 mu m cyclopiazonic acid) had the opposite effect. In conclusion, the data provide experimental evidence that local Ca2+ uptake by SERCA into the SR facilitates the propagation of cytosolic Ca2+ waves via luminal sensitization of the RyR, and supports a novel paradigm of a fire-diffuse-uptake-fire mechanism for Ca2+ wave propagation in cardiac myocytes.