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链脲佐菌素诱导糖尿病大鼠心内膜和心外膜心室肌细胞的钙信号。

Calcium signaling in endocardial and epicardial ventricular myocytes from streptozotocin-induced diabetic rats.

机构信息

Department of Health Sciences, College of Natural and Health Sciences, Zayed University, Abu Dhabi, United Arab Emirates.

Department of Cellular Membranology, Bogomoletz Institute of Physiology, Kiev, Ukraine.

出版信息

J Diabetes Investig. 2021 Apr;12(4):493-500. doi: 10.1111/jdi.13451. Epub 2020 Nov 30.

Abstract

AIMS/INTRODUCTION: Abnormalities in Ca signaling have a key role in hemodynamic dysfunction in diabetic heart. The purpose of this study was to explore the effects of streptozotocin (STZ)-induced diabetes on Ca signaling in epicardial (EPI) and endocardial (ENDO) cells of the left ventricle after 5-6 months of STZ injection.

MATERIALS AND METHODS

Whole-cell patch clamp was used to measure the L-type Ca channel (LTCC) and Na /Ca exchanger currents. Fluorescence photometry techniques were used to measure intracellular free Ca concentration.

RESULTS

Although the LTCC current was not significantly altered, the amplitude of Ca transients increased significantly in EPI-STZ and ENDO-STZ compared with controls. Time to peak LTCC current, time to peak Ca transient, time to half decay of LTCC current and time to half decay of Ca transients were not significantly changed in EPI-STZ and ENDO-STZ myocytes compared with controls. The Na /Ca exchanger current was significantly smaller in EPI-STZ and in ENDO-STZ compared with controls.

CONCLUSIONS

STZ-induced diabetes resulted in an increase in amplitude of Ca transients in EPI and ENDO myocytes that was independent of the LTCC current. Such an effect can be attributed, at least in part, to the dysfunction of the Na /Ca exchanger. Additional studies are warranted to improve our understanding of the regional impact of diabetes on Ca signaling, which will facilitate the discovery of new targeted treatments for diabetic cardiomyopathy.

摘要

目的/引言:钙信号异常在糖尿病心脏的血流动力学功能障碍中起关键作用。本研究的目的是探讨链脲佐菌素(STZ)诱导的糖尿病对 STZ 注射后 5-6 个月左心室心外膜(EPI)和心内膜(ENDO)细胞钙信号的影响。

材料和方法

全细胞膜片钳技术用于测量 L 型钙通道(LTCC)和 Na+/Ca2+交换电流。荧光光度法技术用于测量细胞内游离 Ca2+浓度。

结果

尽管 LTCC 电流没有明显改变,但与对照组相比,EPI-STZ 和 ENDO-STZ 的 Ca 瞬变幅度明显增加。EPI-STZ 和 ENDO-STZ 心肌细胞的 LTCC 电流峰值时间、Ca 瞬变峰值时间、LTCC 电流半衰减时间和 Ca 瞬变半衰减时间与对照组相比没有明显变化。与对照组相比,EPI-STZ 和 ENDO-STZ 的 Na+/Ca2+交换电流明显减小。

结论

STZ 诱导的糖尿病导致 EPI 和 ENDO 心肌细胞 Ca 瞬变幅度增加,而与 LTCC 电流无关。这种作用至少部分归因于 Na+/Ca2+交换器的功能障碍。需要进一步的研究来加深我们对糖尿病对钙信号区域性影响的理解,这将有助于发现治疗糖尿病心肌病的新靶向治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15bc/8015823/f92d9cf58ccc/JDI-12-493-g001.jpg

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