SAH-induced suppression of voltage-gated K(+) (K (V)) channel currents in parenchymal arteriolar myocytes involves activation of the HB-EGF/EGFR pathway.
SAH-induced suppression of voltage-gated K(+) (K (V)) channel currents in parenchymal arteriolar myocytes involves activation of the HB-EGF/EGFR pathway.
复制标题
DOI：
10.1007/978-3-7091-1192-5_34
复制
发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Wellman, George C.
中科院分区：
文献类型：
--
作者：
Koide, Masayo;Wellman, George C.
关键词：
钾离子通道在动脉张力的调节中起重要作用，这些离子通道的活性降低与蛛网膜下腔出血（SAH）后软脑膜动脉血管痉挛有关。我们以前的工作表明，急性应用血液成分，氧合血红蛋白，通过肝素结合表皮生长因子样生长因子（HB-EGF）介导的表皮生长因子受体（EGFR）的激活引起电压门控K+（KV）通道的抑制。使用膜片钳电生理学，我们现在已经研究了在长期体内暴露于蛛网膜下腔血液后，是否在实质小动脉肌细胞中激活KV通道抑制的这一途径。我们已经发现，KV电流，但不是大电导钙激活或内向整流K+通道电流，在实质小动脉心肌细胞新鲜分离的第5天SAH模型兔。有趣的是，与软脑膜动脉肌细胞（IC 50：2.4 ±1.3 ng/mL）相比，对照动物的实质小动脉肌细胞对外源性HB-EGF（IC 50：0.2 ± 0.4 ng/mL）更敏感。然而，HB-EGF和氧合血红蛋白未能降低SAH动物的实质小动脉肌细胞的KV电流，与SAH的EGFR激活和KV电流抑制一致。这些数据表明，HB-EGF/EGFR通路激活有助于KV电流抑制和增强SAH后的实质小动脉收缩。
Potassium channels play an important role in the regulation of arterial tone and decreased activity of these ion channels has been linked to pial artery vasospasm after subarachnoid hemorrhage (SAH). Our previous work has shown that acute application of a blood component, oxyhemoglobin, caused suppression of voltage-gated K+ (KV) channels through heparin-binding epidermal growth factor-like growth factor (HB-EGF) mediated activation of epidermal growth factor receptor (EGFR). Using patch clamp electrophysiology, we have now examined whether this pathway of KV channel suppression is activated in parenchymal arteriolar myocytes following long-term in vivo exposure to subarachnoid blood. We have found that KV currents, but not large conductance Ca2+ activated or inwardly rectifying K+ channel currents, were decreased in parenchymal arteriolar myocytes freshly isolated from Day-5 SAH model rabbits. Interestingly, parenchymal arteriolar myocytes from control animals were more sensitive to exogenous HB-EGF (IC50: 0.2 ± 0.4 ng/mL) compared to pial arterial myocytes (IC50: 2.4 ±1.3 ng/mL). However, HB-EGF and oxyhemoglobin failed to decrease KV currents in parenchymal arteriolar myocytes from SAH animals, consistent with EGFR activation and KV current suppression by SAH. These data suggest that HB-EGF/EGFR pathway activation contributes to KV current suppression and enhanced parenchymal arteriolar constriction after SAH.
登录
查看更多内容
影响因子：
3
作者：
Cipolla, MJ;Li, R;Vitullo, L
通讯作者：
Vitullo, L
DOI：
10.1152/ajpheart.00629.2002
发表时间：
2002-12-01
影响因子：
4.8
作者：
Ishiguro, M;Puryear, CB;Wellman, GC
通讯作者：
Wellman, GC
DOI：
10.1006/bbrc.2002.6720
发表时间：
2002-04-05
影响因子：
3.1
作者：
Matsumoto, S;Kishida, K;Matsuzawa, Y
通讯作者：
Matsuzawa, Y
影响因子：
6.3
作者：
Koide, Masayo;Nystoriak, Matthew A.;Wellman, George C.
通讯作者：
Wellman, George C.
影响因子：
8.3
作者：
Quan, L;Sobey, CG
通讯作者：
Sobey, CG