Diabetes Upregulates BKCa Channels in Pulmonary Arterial Smooth Muscle by Altering the Local Control Mechanism of the Pore-Gate Domain

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation Pub Date : 2026-06-28 DOI:10.1111/micc.70077

Vadym Sydorenko, Irina Ivanova, Dariia Dryn, Mariia Melnyk, Oleksiy Boldyriev, Anatoly Soloviev

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引用次数: 0

Abstract

Objective

Large conductance calcium-activated potassium channels (BK_Ca) play an important role in the regulation of vascular tone. However, the properties of BK_Ca channels in smooth muscle of pulmonary arteries are poorly understood. Previous experimental studies demonstrated that pulmonary hypoxic vasoconstriction as a normal physiological response to decreased oxygen levels was impaired in diabetic animals due to abnormal activation of BK_Ca channels. The aim of this study was to identify mechanisms of diabetes-induced activation of BK_Ca channels in freshly isolated smooth muscle cells from rat pulmonary arteries.

Methods

Type 1 diabetes was induced by streptozotocin (STZ). Whole-cell potassium currents were recorded using the patch-clamp method. Expression levels of BK-α and BK-β1 subunits were measured by real-time PCR.

Results

Our results demonstrate that the amplitude of whole-cell current through BK_Ca channels in rat pulmonary artery smooth muscle cells is significantly increased during STZ-induced diabetes without altering the expression of BK-α and BK-β1 subunits and channel calcium sensitivity. The slow component of BK_Ca current deactivation time constant and spontaneous transient outward current amplitude were increased in diabetic animals compared to healthy animals.

Conclusions

We conclude that abnormal activation of the BK_Ca channel in pulmonary arterial smooth muscle during diabetes is associated with alterations in the local control mechanism of the BK_Ca pore-gate domain.

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糖尿病通过改变孔门结构域的局部控制机制上调肺动脉平滑肌中的BKCa通道。

目的：大电导钙活化钾通道（BKCa）在血管张力调节中发挥重要作用。然而，对肺动脉平滑肌中BKCa通道的特性了解甚少。先前的实验研究表明，肺缺氧血管收缩作为氧水平降低的正常生理反应，在糖尿病动物中由于BKCa通道的异常激活而受损。本研究的目的是确定糖尿病诱导的大鼠肺动脉新鲜分离平滑肌细胞中BKCa通道激活的机制。方法：采用链脲佐菌素（STZ）诱导1型糖尿病。采用膜片钳法记录全细胞钾电流。实时荧光定量PCR检测BK-α和BK-β1亚基的表达水平。结果：stz诱导的糖尿病大鼠肺动脉平滑肌细胞BKCa通道全细胞电流振幅显著增加，但BK-α和BK-β1亚基的表达和通道钙敏感性均未发生改变。糖尿病动物BKCa电流失活慢速分量时间常数和自发瞬态外向电流幅值均高于健康动物。结论：糖尿病患者肺动脉平滑肌中BKCa通道的异常激活与BKCa孔门结构域局部控制机制的改变有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Microcirculation 医学-外周血管病

CiteScore

5.00

自引率

4.20%

发文量

审稿时长

6-12 weeks

期刊介绍： The journal features original contributions that are the result of investigations contributing significant new information relating to the vascular and lymphatic microcirculation addressed at the intact animal, organ, cellular, or molecular level. Papers describe applications of the methods of physiology, biophysics, bioengineering, genetics, cell biology, biochemistry, and molecular biology to problems in microcirculation. Microcirculation also publishes state-of-the-art reviews that address frontier areas or new advances in technology in the fields of microcirculatory disease and function. Specific areas of interest include: Angiogenesis, growth and remodeling; Transport and exchange of gasses and solutes; Rheology and biorheology; Endothelial cell biology and metabolism; Interactions between endothelium, smooth muscle, parenchymal cells, leukocytes and platelets; Regulation of vasomotor tone; and Microvascular structures, imaging and morphometry. Papers also describe innovations in experimental techniques and instrumentation for studying all aspects of microcirculatory structure and function.