Nikmaram Mohammed R, Liu Jie, Abdelrahman Mohamed, Dobrzynski Halina, Boyett Mark R, Lei Ming
Department of Physiology, Iran University of Medical Sciences, Tehran, Iran.
Prog Biophys Mol Biol. 2008 Jan-Apr;96(1-3):452-64. doi: 10.1016/j.pbiomolbio.2007.07.003. Epub 2007 Aug 1.
To characterize the effects of inhibition of Ryanodine receptor (RyR), TTX-sensitive neuronal Na+ current (iNa), "rapidly activating" delayed rectifier K+ current (iKr) and ultrarapid delayed rectifier potassium current (IKur) on the pacemaker activity of the sinoatrial node (SAN) and the atrioventricular node (AVN) in the mouse.
The structure of mouse AVN was studied by histology and immunolabelling of Cx43 and hyperpolarization-activated, cyclic nucleotide-binding channels (HCN). The effects of Ryanodine, TTX, E-4031 and 4-AP on pacemaker activities recorded from mouse intact SAN and AVN preparations have been investigated.
Immuno-histological characterization delineated the structure of the AVN showing the similar molecular phenotype of the SAN. The effects of these inhibitors on the cycle length (CL) of the spontaneous pacemaker activity of the SAN and the AVN were characterized. Inhibition of RyR by 0.2 and 2 microM Ryanodine prolonged CL by 42+/-12.3% and 64+/-18.1% in SAN preparations by 163+/-72.3% and 241+/-91.2% in AVN preparations. Inhibition of TTX-sensitive iNa by 100 nM TTX prolonged CL by 22+/-6.0% in SAN preparations and 53+/-13.6% in the AVN preparations. Block of iKr by E-4031 prolonged CL by 68+/-12.5% in SAN preparations and 28+/-3.4% in AVN preparations. Inhibition of iKur by 50 microM 4-AP prolonged CL by 20+/-3.4% in SAN preparations and 18+/-3.0% in AVN preparations.
Mouse SAN and AVN showed distinct different response to the inhibition of RyR, TTX-sensitive INa, IKr and iKur, which reflects the variation in contribution of these currents to the pacemaker function of the cardiac nodes in the mouse. Our data provide valuable information for developing virtual tissue models of mouse SAN and AVN.
研究抑制兰尼碱受体（RyR）、河豚毒素敏感的神经元钠电流（iNa）、“快速激活”延迟整流钾电流（iKr）和超快速延迟整流钾电流（IKur）对小鼠窦房结（SAN）和房室结（AVN）起搏活动的影响。
通过组织学以及连接蛋白43（Cx43）和超极化激活的环核苷酸结合通道（HCN）的免疫标记研究小鼠房室结的结构。研究了兰尼碱、河豚毒素、E-4031和4-氨基吡啶（4-AP）对从小鼠完整窦房结和房室结标本记录的起搏活动的影响。
免疫组织学特征描绘了房室结的结构，显示出与窦房结相似的分子表型。表征了这些抑制剂对窦房结和房室结自发起搏活动的周期长度（CL）的影响。在窦房结标本中，0.2微摩尔和2微摩尔兰尼碱抑制RyR使CL分别延长42±12.3%和64±18.1%，在房室结标本中分别延长163±72.3%和241±91.2%。100纳摩尔河豚毒素抑制河豚毒素敏感的iNa使窦房结标本中的CL延长22±6.0%，在房室结标本中延长53±13.6%。E-4031阻断iKr使窦房结标本中的CL延长68±12.5%，在房室结标本中延长28±3.4%。50微摩尔4-AP抑制IKur使窦房结标本中的CL延长20±3.4%，在房室结标本中延长18±3.0%。
小鼠窦房结和房室结对RyR、河豚毒素敏感的INa、IKr和IKur抑制表现出明显不同的反应，这反映了这些电流对小鼠心脏节点起搏功能贡献的差异。我们的数据为开发小鼠窦房结和房室结的虚拟组织模型提供了有价值的信息。
