Electrophysiological characteristics of heart ventricular  papillary muscles in diabetic histidine decarboxylase  knockout and wild-type mice.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Szebeni
Andrea
A
Department of Pharmacology and Pharmacotherapy, Semmelweis University, PO Box 370, 1445 Budapest, Hungary.
Falus
András
A
Kecskeméti
Valéria
V
D000818:Animals; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000503:physiopathology*; D006329:Heart Conduction System / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology*; D006640:Histidine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010210:Papillary Muscles / Q000503:physiopathology*; D013311:Streptozocin
D013311:Streptozocin; D006640:Histidine Decarboxylase