首页> 美国卫生研究院文献>American Journal of Physiology - Heart and Circulatory Physiology >Interactions between adenosine and K+ channel-related pathways in the coupling of somatosensory activation and pial arteriolar dilation
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Interactions between adenosine and K+ channel-related pathways in the coupling of somatosensory activation and pial arteriolar dilation

机译:体感激活与心房小动脉扩张耦合中腺苷和K +通道相关通路之间的相互作用

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摘要

Multiple, perhaps interactive, mechanisms participate in the linkage between increased neural activity and cerebral vasodilation. In the present study, we assessed whether neural activation-related pial arteriolar dilation (PAD) involved interactions among adenosine (Ado) A2 receptors (A2Rs), large-conductance Ca2+-operated K+ (BKCa) channels, and inward rectifier K+ (Kir) channels. In rats with closed cranial windows, we monitored sciatic nerve stimulation (SNS)-induced PAD in the absence or presence of pharmacological blockade of A2Rs (ZM-241385), ecto-5′-nucleotidase (α,β-methylene-adenosine diphosphate), BKCa channels (paxilline), and Kir channels (BaCl2). Individually, these interventions led to 53–66% reductions in SNS-induced PADs. Combined applications of these blockers led to little or no further repression of SNS-induced PADs, suggesting interactions among A2Rs and K+ channels. In the absence of SNS, BaCl2 blockade of Kir channels produced 52–80% reductions in Ado and NS-1619 (BKCa channel activator)-induced PADs. In contrast, paxilline blockade of BKCa channels was without effect on dilations elicited by KCl (Kir channel activator) and Ado suffusions, indicating that Ado- and NS-1619-associated PADs involved Kir channels. In addition, targeted ablation of the superficial glia limitans was associated with a selective 60–80% loss of NS-1619 responses, suggesting that the BKCa channel participation (and paxilline sensitivity) derived largely from channels within the glia limitans. Additionally, blockade of either PKA or adenylyl cyclase caused markedly attenuated pial arteriolar responses to SNS and, in the absence of SNS, responses to Ado, KCl, and NS-1619. These findings suggested a key, possibly permissive, role for A2R-linked cAMP generation and PKA-induced K+ channel phosphorylation in somatosensory activation-evoked PAD.
机译:多种可能相互作用的机制参与了神经活动增加与脑血管舒张之间的联系。在本研究中,我们评估了神经激活相关的椎小动脉扩张(PAD)是否涉及腺苷(Ado)A2受体(A2Rs),大电导Ca 2 + 操作的K 之间的相互作用+ (BKCa)通道和向内整流器K + (Kir)通道。在闭合颅窗的大鼠中,我们在不存在或存在A2Rs(ZM-241385),ecto-5'-核苷酸酶(α,β-亚甲基-腺苷二磷酸)药理学阻滞的情况下,监测坐骨神经刺激(SNS)诱导的PAD。 ,BKCa通道(paxilline)和Kir通道(BaCl2)。这些干预措施单独导致SNS诱导的PAD降低53–66%。这些阻滞剂的联合使用导致SNS诱导的PAD抑制得很少甚至没有,这表明A2R和K + 通道之间存在相互作用。在没有SNS的情况下,BaCl2阻断Kir通道可使Ado和NS-1619(BKCa通道激活剂)诱导的PAD减少52-80%。相反,对BKCa通道的茶碱阻断对KCl(Kir通道激活剂)和Ado注入引起的扩张没有影响,这表明与Ado和NS-1619相关的PAD涉及Kir通道。此外,靶向消融浅表神经胶质限脂蛋白与选择性降低60%至80%的NS-1619反应有关,这表明BKCa通道参与(和paxilline敏感性)主要源自胶质限脂蛋白内的通道。此外,对PKA或腺苷酸环化酶的阻断都会导致对SNS的小动脉运动明显减弱,在不存在SNS的情况下,对Ado,KCl和NS-1619的响应也会减弱。这些发现表明,在体感激活诱发的PAD中,A 2 R连接的cAMP的产生和PKA诱导的K + 通道磷酸化起着关键性的作用。

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