Heart Rate and Extracellular Sodium and Potassium Modulation of Gap Junction Mediated Conduction in Guinea Pigs.
Heart Rate and Extracellular Sodium and Potassium Modulation of Gap Junction Mediated Conduction in Guinea Pigs.
复制标题
DOI：
10.3389/fphys.2016.00016
复制
发表时间：
2016
影响因子：
4
通讯作者：
Poelzing S
中科院分区：
文献类型：
--
作者：
Entz M 2nd;George SA;Zeitz MJ;Raisch T;Smyth JW;Poelzing S
背景资料：最近的研究表明，在具有狭窄的perinexi和50%的连接蛋白43（Cx43）表达减少的小鼠心脏中，心脏传导对细胞外钾（[K+]o）和钠（[Na+]o）的相对生理变化更敏感。目的：确定相似的[K+]o和[Na+]o变化是否改变豚鼠中传导速度（CV）对药理学间隙连接（GJ）解偶联的敏感性。研究方法：在Langendorff灌注的豚鼠心室中[K+]o和[Na+]o变化（溶液A：[K+]o = 4.56和[Na+]o = 153.3 mM。溶液B：[K+]o = 6.95和[Na+]o = 145.5 mM）。用甘珀酸（CBX）（15和30 μM）抑制间隙连接。心外膜CV通过光学标测进行定量。用透射电子显微镜测量围缘宽度。通过蛋白质印迹法评估总Cx43和磷酸化Cx43。结果：在对照条件下或使用15μM CBX时，溶液组成未改变CV。将起搏的基本周期长度（BCL）从300 ms降低至160 ms，两种解决方案的CV均降低。在30 μM CBX时，在BCL = 300 ms时，溶液的变化不会纵向或横向改变CV。然而，将BCL降至160 ms会导致用溶液B灌注的心脏的CV比A灌注的心脏降低更多。解决方案的组合物没有改变perinexal宽度，也没有改变总或磷酸化丝氨酸368 Cx43的表达。这些数据表明，溶液依赖性CV的变化是独立的改变perinexal宽度或GJ耦合。与溶液A相比，溶液B灌注心脏的动作电位持续时间始终较短，与起搏频率和/或CBX浓度无关。结论：心率增加和GJ解偶联可以揭示由[K+]o和[Na+]o变化引起的CV小差异。这些数据表明，调节细胞外离子组成可能是一种新的抗心律失常的目标，在疾病与异常GJ耦合，特别是当心率无法控制。
Background: Recent studies suggested that cardiac conduction in murine hearts with narrow perinexi and 50% reduced connexin43 (Cx43) expression is more sensitive to relatively physiological changes of extracellular potassium ([K+]o) and sodium ([Na+]o). Purpose: Determine whether similar [K+]o and [Na+]o changes alter conduction velocity (CV) sensitivity to pharmacologic gap junction (GJ) uncoupling in guinea pigs. Methods: [K+]o and [Na+]o were varied in Langendorff perfused guinea pig ventricles (Solution A: [K+]o = 4.56 and [Na+]o = 153.3 mM. Solution B: [K+]o = 6.95 and [Na+]o = 145.5 mM). Gap junctions were inhibited with carbenoxolone (CBX) (15 and 30 μM). Epicardial CV was quantified by optical mapping. Perinexal width was measured with transmission electron microscopy. Total and phosphorylated Cx43 were evaluated by western blotting. Results: Solution composition did not alter CV under control conditions or with 15μM CBX. Decreasing the basic cycle length (BCL) of pacing from 300 to 160 ms decreased CV uniformly with both solutions. At 30 μM CBX, a change in solution did not alter CV either longitudinally or transversely at BCL = 300 ms. However, reducing BCL to 160 ms caused CV to decrease more in hearts perfused with Solution B than A. Solution composition did not alter perinexal width, nor did it change total or phosphorylated serine 368 Cx43 expression. These data suggest that the solution dependent CV changes were independent of altered perinexal width or GJ coupling. Action potential duration was always shorter in hearts perfused with Solution B than A, independent of pacing rate and/or CBX concentration. Conclusions: Increased heart rate and GJ uncoupling can unmask small CV differences caused by changing [K+]o and [Na+]o. These data suggest that modulating extracellular ionic composition may be a novel anti-arrhythmic target in diseases with abnormal GJ coupling, particularly when heart rate cannot be controlled.