Barajas-Martinez Hector, Goodrow Robert J, Hu Dan, Patel Payal, Desai Mayurika, Panama Brian K, Treat Jacqueline A, Aistrup Gary L, Cordeiro Jonathan M
Department of Experimental Cardiology, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY, 13501, USA.
Pflugers Arch. 2017 Jun;469(5-6):703-712. doi: 10.1007/s00424-017-1956-4. Epub 2017 Feb 27.
The collar of the pulmonary vein (PV) is the focal point for the initiation of atrial arrhythmias, but the mechanisms underlying how PV cells differ from neighboring left atrial tissue are unclear. We examined the biophysical and molecular properties of I in cells isolated from the canine pulmonary sleeve and compared the properties to left atrial tissue. PV and left atrial myocytes were isolated and patch clamp techniques were used to record I. Action potential recordings from either tissue type were made using high-resistance electrodes. mRNA was determined using quantitative RT-PCR and proteins were determined by Western blot. Analysis of the action potential characteristics showed that PV tissue had a lower Vmax compared with left atrial tissue. Fast I showed that current density was slightly lower in PV cells compared with LA cells (-96 ± 18.7 pA/pF vs. -120 ± 6.7 pA/pF, respectively, p < 0.05). The recovery from inactivation of I in PV cells was slightly slower but no marked difference in steady-state inactivation was noted. Analysis of late I during a 225-ms pulse showed that late I was significantly smaller in PV cells compared to LA cells at all measured time points into the pulse. These results suggest PV cells have lower density of both peak and late I. Molecular analysis of Nav1.5 and the four beta subunits showed lower levels of Nav1.5 as well as Navβ1 subunits, confirming the biophysical findings. These data show that a lower density of I may lead to depression of excitability and predispose the PV collar to re-entrant circuits under pathophysiological conditions.
肺静脉（PV）的边缘是房性心律失常起始的焦点，但PV细胞与相邻左心房组织不同的潜在机制尚不清楚。我们研究了从犬肺袖套分离的细胞中I的生物物理和分子特性，并将这些特性与左心房组织进行了比较。分离出PV和左心房心肌细胞，采用膜片钳技术记录I。使用高电阻电极记录两种组织类型的动作电位。使用定量逆转录聚合酶链反应测定mRNA，通过蛋白质印迹法测定蛋白质。动作电位特征分析表明，与左心房组织相比，PV组织的最大上升速率较低。快速I显示，与左心房（LA）细胞相比，PV细胞中的电流密度略低（分别为-96±18.7 pA/pF和-120±6.7 pA/pF，p<0.05）。PV细胞中I从失活状态恢复的速度略慢，但稳态失活没有明显差异。在225毫秒脉冲期间对晚期I的分析表明，在脉冲的所有测量时间点，PV细胞中的晚期I明显小于LA细胞。这些结果表明，PV细胞的峰值I和晚期I密度均较低。对Nav1.5和四个β亚基的分子分析显示，Nav1.5以及Navβ1亚基的水平较低，证实了生物物理研究结果。这些数据表明，较低密度的I可能导致兴奋性降低，并使PV边缘在病理生理条件下易发生折返环路。
