Propagation of pacemaker activity in the guinea-pig antrum
Propagation of pacemaker activity in the guinea-pig antrum
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DOI：
10.1113/jphysiol.2003.059055
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发表时间：
2004-04-15
影响因子：
5.5
通讯作者：
Smith, TK
中科院分区：
文献类型：
--
作者：
Hennig, GW;Hirst, GDS;Smith, TK
周期性的去极化（慢波）是胃窦内混合和排空内容物的蠕动收缩的基础。慢波起源于Cajal间质细胞的肌间网络（ICC-MY）。在这项研究中，我们可视化了与起搏器电位相关的钙离子瞬态在离体豚鼠胃窦的ICC网络和纵向（LM）和圆形肌肉（CM）层的序列和传播。解剖胃窦，显示ICC-MY网络，加载Fluo-4 AM，并在37°c下监测活动。Ca2+波以3.24 +/- 0.12 mm s（-1）的平均速度以4.87 +/- 0.16 cycles min（-1）的频率在ICC-MY网络中传播（n = 4）。Ca2+波的传播通常呈现“阶梯状”，网络的不同区域在不同的延迟后被激活。繁殖方向变化很大（繁殖角度为每周期44.3 +/- 10.9度），不局限于纵肌或圆形肌的轴线。Ca2+波似乎从起始部位呈放射状扩散。ICC-MY的起始Ca2+波与Cajal、ICC-IM和平滑肌细胞肌内间质细胞的继发性Ca2+波以及视场局部畸变（收缩）相关。TTX （1 muM）对慢波或起搏器电位活动的影响很小，但2-APB （50 muM）阻断了所有Ca2+波，表明细胞内Ca2+储存的关键作用。尼卡地平（2mum）消除了平滑肌产生的Ca2+瞬态，但不影响ICC-MY相关的快速上冲。这些结果表明，慢波遵循一系列激活，从ICC-MY和ICC-IM网络开始，随后是负责收缩的肌肉层中持续的Ca2+瞬态。
Cyclical periods of depolarization (slow waves) underlie peristaltic contractions involved in mixing and emptying of contents in the gastric antrum. Slow waves originate from a myenteric network of interstitial cells of Cajal (ICC-MY). In this study we have visualized the sequence and propagation of Ca2+ transients associated with pacemaker potentials in the ICC network and longitudinal (LM) and circular muscle (CM) layers of the isolated guinea-pig gastric antrum. Gastric antrum was dissected to reveal the ICC-MY network, loaded with Fluo-4 AM and activity was monitored at 37degreesC. Ca2+ waves propagated throughout the ICC-MY network at an average velocity of 3.24 +/- 0.12 mm s(-1) at a frequency of 4.87 +/- 0.16 cycles min(-1) (n = 4). The propagation of the Ca2+ wave often appeared 'step-like', with separate regions of the network being activated after variable delays. The direction of propagation was highly variable (A angle of propagation 44.3 +/- 10.9 deg per cycle) and was not confined to the axes of the longitudinal or circular muscle. Ca2+ waves appeared to spread out radially from the site of initiation. The initiating Ca2+ wave in ICC-MY was correlated to secondary Ca2+ waves in intramuscular interstial cells of Cajal, ICC-IM, and smooth muscle cells, and the local distortion (contraction) in a field of view. TTX (1 muM) had little effect on slow wave or pacemaker potential activity, but 2-APB (50 muM) blocked all Ca2+ waves, indicating a pivotal role for intracellular Ca2+ stores. Nicardipine (2 muM) eliminated the Ca2+ transient generated by smooth muscle, but did not affect the fast upstroke associated with ICC-MY. These results indicate that slow waves follow a sequence of activation, beginning with the ICC-MY and ICC-IM network, followed later by a sustained Ca2+ transient in the muscle layers that is responsible for contraction.