Szebeni Andrea, Falus András, Kecskeméti Valéria
Department of Pharmacology and Pharmacotherapy, Semmelweis University, PO Box 370, 1445 Budapest, Hungary.
J Interv Card Electrophysiol. 2009 Dec;26(3):155-8. doi: 10.1007/s10840-009-9432-5.
The diabetes-induced action potential (AP) abnormalities have been studied mainly in rats where significant prolongation of repolarization and reduced maximum rate of depolarization (Vmax) was detected. Histidine decarboxylase knockout (HDC-KO) mice lack endogenous histamine and they are characterized by impaired glucose tolerance. Furthermore they have autoantibodies reactive to glutamic acid decarboxylase (GAD). These findings suggested that this model might have an increased susceptibility to autoimmune diabetes.
Standard microelectrode technique was used to characterise the cardiac electrophysiological parameters of control and Streptozotocin (STZ) induced diabetic HDC-KO mice comparing with those of wild type animals.
With aging, blood glucose levels in HDC-KO mice were shifted towards values characteristic of diabetes. The electrophysiological changes relevant to diabetes i.e. prolongation of repolarization and depression of Vmax developed without any induction with STZ. In this group STZ treatment caused no further significant AP changes.
One of the likely explanations may be that in the chain of events in HDC-KO mice on the one hand and in Streptozotocin-induced diabetes on the other hand, leading to the alterations in the heart electrophysiological parameters, there is a common link. This link may be a similar shift in the expression/function of certain K+ channel populations.
糖尿病诱导的动作电位(AP)异常主要在大鼠中进行了研究,在这些大鼠中检测到复极化显著延长和最大去极化速率(Vmax)降低。组氨酸脱羧酶基因敲除(HDC-KO)小鼠缺乏内源性组胺,其特征为糖耐量受损。此外,它们具有对谷氨酸脱羧酶(GAD)有反应的自身抗体。这些发现表明该模型可能对自身免疫性糖尿病易感性增加。
采用标准微电极技术,将对照和链脲佐菌素(STZ)诱导的糖尿病HDC-KO小鼠的心脏电生理参数与野生型动物进行比较。
随着年龄增长,HDC-KO小鼠的血糖水平向糖尿病特征值偏移。与糖尿病相关的电生理变化,即复极化延长和Vmax降低,在未用STZ诱导的情况下就已出现。在该组中,STZ治疗未引起AP进一步显著变化。
一种可能的解释可能是,一方面在HDC-KO小鼠的事件链中,另一方面在链脲佐菌素诱导的糖尿病中,导致心脏电生理参数改变的过程中存在一个共同环节。这个环节可能是某些钾通道群体的表达/功能发生了类似的变化。