Reduced expression of HCN channels in the sinoatrial node of streptozotocin-induced diabetic rats
Reduced expression of HCN channels in the sinoatrial node of streptozotocin-induced diabetic rats
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DOI：
10.1139/cjpp-2016-0418
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发表时间：
2017-05-01
影响因子：
2.1
通讯作者：
Guo, Ning
中科院分区：
文献类型：
--
作者：
Huang, Xin;Zhong, Nier;Guo, Ning
糖尿病（DM）与心脏的电重构有关，增加了心律失常的风险。然而，在窦房结（SAN）的DM的电重构的知识是有限的。我们研究了HCN通道亚型HCN 1-HCN 4在链脲佐菌素（STZ）诱导的糖尿病大鼠和年龄匹配的对照组SAN中的表达。我们发现，STZ诱导的糖尿病大鼠具有较低的固有心率，窦房传导时间延长，率校正的最大窦房结恢复时间在体内以及更长的周期长度（CL）在体外，与对照组相比。SAN的光学标测表明，较低的领先的起搏器网站，降低SAN传导速度和舒张期去极化斜率，和较长的动作电位时程在STZ诱导的糖尿病大鼠比在对照组。糖尿病SAN中HCN 2和HCN 4的转录和蛋白表达减少。3 μ mol/L伊伐布雷定特异性阻断HCN通道可显著延长糖尿病大鼠Langendorff心脏的CL 18%和对照组的CL 26%。HCN通道亚型在STZ诱导的糖尿病大鼠SAN中的表达减少可能是DM中SAN功能降低的重要贡献者。
Diabetes mellitus (DM) is associated with an electrical remodeling of the heart, increasing the risk of arrhythmias. However, knowledge of electrical remodeling in the sinoatrial node (SAN) by DM is limited. We investigated the expression of HCN channel isoforms, HCN1-HCN4, in SAN from streptozotocin (STZ)-induced diabetic rats and the age-matched controls. We found that the STZ-induced diabetic rats have a lower intrinsic heart rate, a lengthened sinoatrial conduction time, and rate-corrected maximal sinoatrial node recovery time in vivo as well as a longer cycle length (CL) in vitro, as compared with the control. Optical mapping of the SAN demonstrated an inferior leading pacemaker site, reduced SAN conduction velocity and diastolic depolarization slope, and a longer action potential duration in the STZ-induced diabetic rats than in the control. The transcripts and proteins of HCN2 and HCN4 in diabetic SAN were reduced. Specific blockade of HCN channels by 3 mu mol/L ivabradine significantly prolonged the CL of a Langendorff heart by 18% in the diabetic rats and 26% in the control. The reduced expression of HCN channel isoforms in the SAN of the STZ-induced diabetic rat may be an important contributor to the reduced SAN function in DM.