期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 28, 期 2, 页码 377-386出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.jcbfm.9600536
关键词
big-conductance; Ca2+-activated K+ channel; gene deletion mouse; patch clamp recording; type-1 diabetes; vascular smooth muscle cell
资金
- NHLBI NIH HHS [R01 HL049426] Funding Source: Medline
Cerebral vascular dysfunction and associated diseases often occur in type-1 diabetes, but the underlying mechanisms are largely unknown. In this study, we sought to determine whether big-conductance, Ca2+-activated K+ (BK) channels were impaired in vascular (cerebral artery) smooth muscle cells (CASMCs) from streptozotocin-induced type-1 diabetic mice using patch clamp, molecular biologic, and genetic approaches. Our data indicate that the frequency and amplitude of spontaneous transient outward currents (STOCs) are significantly decreased, whereas the activity of spontaneous Ca2+ sparks is increased, in diabetic CASMCs. The sensitivity of BK channels to voltage, Ca2+, and the specific inhibitor iberiotoxin are all reduced in diabetic myocytes. Diabetic mice show increased myogenic tone and decreased contraction in response to iberiotoxin in cerebral arteries and elevated blood pressure. The expression of the BK channel beta 1, but not alpha-subunit protein, is markedly decreased in diabetic cerebral arteries. Diabetic impairment of BK channel activity is lost in CASMCs from BK channel beta 1-subunit gene deletion mice. In conclusion, the BK channel beta 1-subunit is impaired in type-1 diabetic vascular SMCs, resulting in increased vasoconstriction and elevated blood pressure, thereby contributing to vascular diseases in type-1 diabetes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据