Electrophysiological mapping of embryonic mouse hearts: mechanisms for developmental pacemaker switch and internodal conduction pathway.
Electrophysiological mapping of embryonic mouse hearts: mechanisms for developmental pacemaker switch and internodal conduction pathway.
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DOI：
10.1111/j.1540-8167.2011.02191.x
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发表时间：
2012-03
影响因子：
2.7
通讯作者：
Chen HS
中科院分区：
文献类型：
--
作者：
Yi T;Wong J;Feller E;Sink S;Taghli-Lamallem O;Wen J;Kim C;Fink M;Giles W;Soussou W;Chen HS
了解窦房结 (SAN) 的发育有助于开发 SAN 功能障碍的治疗方法。然而，SAN 发育的电生理学研究仍然很困难，因为 SAN 功能障碍的突变小鼠通常是胚胎致死的。因此，大多数关于 SAN 开发的研究仅限于免疫细胞化学观察，而没有可比的功能研究。我们应用多电极阵列 (MEA) 记录系统来研究在胚胎年龄 (E) 8.5 至 12.5 天时急性分离的小鼠心脏中 SAN 的发育。定期恢复生理心率，从而能够准确评估 SAN 发育的功能。我们发现，主要起搏活动在 E8.5 时起源于左流入道 (LIFT) 区域，但在 E12.5 时切换到右 SAN。结合 MEA 记录和药物制剂，我们发现细胞内钙 (Ca2+) 介导的自动性发展较早，并且是 E8.5 心脏 LIFT 中脉冲生成的主要机制。在 E12.5 的后期开发中，当起搏器通道在 LIFT 中下调时，肌膜离子通道在 SAN 中发育，导致起搏器的主要位置发生变化。此外，低微摩尔浓度的河豚毒素 (TTX)（一种钠通道阻滞剂）对 E8.5–12.5 的起搏器节律影响最小；但抑制心房激活并揭示了介导 E12.5 心脏中结间传导的抗河豚毒素 SAN-房室结（结间）通路。使用生理映射方法，我们证明左右流入道区域之间的自动化差异机制发展赋予起搏器位置切换。此外，河豚毒素抗性途径介导 E12.5 小鼠心脏中的优先节间传导。
Understanding sinoatrial node (SAN) development could help in developing therapies for SAN dysfunction. However, electrophysiological investigation of SAN development remains difficult because mutant mice with SAN dysfunctions are frequently embryonically lethal. Most research on SAN development is therefore limited to immunocytochemical observations without comparable functional studies. We applied a multi-electrode array (MEA) recording system to study SAN development in mouse hearts acutely isolated at embryonic ages (E) 8.5 to 12.5 days. Physiological heart rates were routinely restored, enabling accurate functional assessment of SAN development. We found that dominant pacemaking activity originated from the left inflow tract (LIFT) region at E8.5, but switched to the right SAN by E12.5. Combining MEA recordings and pharmacological agents, we show that intracellular calcium (Ca2+)-mediated automaticity develops early and is the major mechanism of pulse generation in the LIFT of E8.5 hearts. Later in development at E12.5, sarcolemmal ion channels develop in the SAN at a time when pacemaker channels are down regulated in the LIFT, leading to a switch in the dominant pacemaker location. Additionally, low micromolar concentrations of tetrodotoxin (TTX), a sodium channel blocker, minimally affect pacemaker rhythm at E8.5–12.5; but suppress atrial activation and reveal a tetrodotoxin-resistant SAN-atrioventricular node (internodal) pathway that mediates internodal conduction in E12.5 hearts. Using a physiological mapping method, we demonstrate that differential mechanistic development of automaticity between the left and right inflow tract regions confers the pacemaker location switch. Moreover, a tetrodotoxin-resistant pathway mediates preferential internodal conduction in E12.5 mouse hearts.
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影响因子：
14.8
作者：
Palmer, Amy E.;Tsien, Roger Y.
通讯作者：
Tsien, Roger Y.
影响因子：
5.5
作者：
HIROTA, A;KAMINO, K;YADA, T
通讯作者：
YADA, T
影响因子：
5
作者：
Viswanathan, S.;Burch, J. B. E.;Benson, D. W.
通讯作者：
Benson, D. W.
DOI：
10.1152/ajpheart.1999.277.6.h2458
发表时间：
1999-12-01
影响因子：
4.8
作者：
Gysembergh, A;Lemaire, S;Przyklenk, K
通讯作者：
Przyklenk, K
影响因子：
3
作者：
BRIGGS, I;BOSMITH, RE;HEAPY, CG
通讯作者：
HEAPY, CG