Pyridine nucleotide redox potential in coronary smooth muscle couples myocardial blood flow to cardiac metabolism.
Pyridine nucleotide redox potential in coronary smooth muscle couples myocardial blood flow to cardiac metabolism.
复制标题
DOI：
10.1038/s41467-022-29745-z
复制
发表时间：
2022-04-19
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
在压力下向心脏输送足够的氧气对维持心脏功能至关重要。心肌需氧量的急性增加通过平滑肌电压门控K+ (Kv)通道的功能上调引起冠状动脉血管舒张并增强灌注。由于这种反应是由Kv1附属亚基（即Kvβ）控制的，这些亚基是NAD(P)(H)依赖的醛酮还原酶，因此我们验证了氧气需求改变动脉[NAD(H)]i的假设，以及由此产生的胞质吡啶核苷酸氧化还原状态影响Kv1活性。高分辨率成像质谱和活细胞成像显示心肌内动脉肌细胞中NADH:NAD+的增加依赖于心脏工作负荷。反映高需氧量的细胞内NAD(P)(H)氧化还原比率以依赖于kv β2的方式增强了天然冠状动脉Kv1活性。消融Kvβ2的催化作用可抑制氧化还原依赖性的Kv1活性、血管舒张以及心脏负荷与心肌血流量之间的关系。总的来说，这项工作表明，在代谢应激期间，Kvβ2的吡啶核苷酸敏感性和酶活性控制冠状动脉血管反应性和心肌血流量。血液流动与心脏对氧需求的生理匹配是维持心脏健康所必需的，但其潜在机制尚不清楚。在这里，作者报告了冠状动脉平滑肌细胞内吡啶核苷酸氧化还原状态的急性修饰及其对代谢性血管舒张中电压门控K +通道的影响的关键作用
Adequate oxygen delivery to the heart during stress is essential for sustaining cardiac function. Acute increases in myocardial oxygen demand evoke coronary vasodilation and enhance perfusion via functional upregulation of smooth muscle voltage-gated K+ (Kv) channels. Because this response is controlled by Kv1 accessory subunits (i.e., Kvβ), which are NAD(P)(H)-dependent aldo-keto reductases, we tested the hypothesis that oxygen demand modifies arterial [NAD(H)]i, and that resultant cytosolic pyridine nucleotide redox state influences Kv1 activity. High-resolution imaging mass spectrometry and live-cell imaging reveal cardiac workload-dependent increases in NADH:NAD+ in intramyocardial arterial myocytes. Intracellular NAD(P)(H) redox ratios reflecting elevated oxygen demand potentiate native coronary Kv1 activity in a Kvβ2-dependent manner. Ablation of Kvβ2 catalysis suppresses redox-dependent increases in Kv1 activity, vasodilation, and the relationship between cardiac workload and myocardial blood flow. Collectively, this work suggests that the pyridine nucleotide sensitivity and enzymatic activity of Kvβ2 controls coronary vasoreactivity and myocardial blood flow during metabolic stress. Physiological matching of blood flow to the demand for oxygen by the heart is required for sustained cardiac health, yet the underlying mechanisms are obscure. Here, the authors report a key role for acute modifications to the redox state of intracellular pyridine nucleotides in coronary smooth muscle and their impact on voltage-gated K + channels in metabolic vasodilation
登录
查看更多内容
影响因子：
5
作者：
El Gebeily, Gracia;El Khoury, Nabil;Fiset, Celine
通讯作者：
Fiset, Celine
DOI：
10.1152/ajpheart.2000.279.6.h2872
发表时间：
2000-12-01
影响因子：
4.8
作者：
Barron, JT;Gu, LP;Parrillo, JE
通讯作者：
Parrillo, JE
影响因子：
56.9
作者：
Long, SB;Campbell, EB;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
--
作者：
KUO, L;DAVIS, MJ;CHILIAN, WM
通讯作者：
CHILIAN, WM
影响因子：
56.9
作者：
Gulbis, JM;Zhou, M;MacKinnon, R
通讯作者：
MacKinnon, R