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首页> 外文期刊>The Journal of Urology >Potassium Channels and Human Corporeal Smooth Muscle Cell Tone: Diabetes and Relaxation of Human Corpus Cavernosum Smooth Muscle by Adenosine Triphosphate Sensitive Potassium Channel Openers.
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Potassium Channels and Human Corporeal Smooth Muscle Cell Tone: Diabetes and Relaxation of Human Corpus Cavernosum Smooth Muscle by Adenosine Triphosphate Sensitive Potassium Channel Openers.

机译：钾通道和人体内平滑肌细胞的音调：糖尿病和人类三体腺苷三磷酸腺苷敏感性钾通道开放剂使人海绵体平滑肌松弛。

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PURPOSE: Sustained contraction of human corporeal smooth muscle depends on continuous transmembrane calcium flux through voltage gated calcium channels. K channels modulate corporeal smooth muscle membrane potential and, thus, ultimately affect transmembrane calcium flux. Therefore, we characterized relaxation responses elicited by the K channel modulators pinacidil and levcromakalim on isolated human corporeal tissue strips. We also evaluated the possibility that there may be alterations in adenosine triphosphate sensitive K channel pharmacology/function related to the presence of diabetes mellitus. MATERIALS AND METHODS: A total of 215 isolated human corporeal tissue strips obtained from 57 male patients with organic erectile dysfunction were investigated. Cumulative concentration-response curves were constructed at half log increments for steady state relaxation responses elicited by pinacidil and levcromakalim on equivalently phenylephrine pre-contracted (to approximately 75% of maximum) isolated corporeal tissue strips. Potassium currents were measured using the cell attached whole cell patch clamp technique on freshly isolated corporeal smooth muscle cells. RESULTS: A concentration dependent, glibenclamide sensitive relaxation response of phenylephrine pre-contracted corporeal tissue strips was observed for pinacidil and levcromakalim. Consistent with such observations, electrophysiological recordings on freshly isolated myocytes revealed that pinacidil (10 &mgr;M.) and levcromakalim (10 &mgr;M.) induced whole cell potassium currents that were blocked by glibenclamide (10 &mgr;M.). In addition, statistical analysis revealed that phenylephrine pre-contracted corporeal tissue strips from patients without diabetes were more sensitive to relaxation by both compounds than corporeal tissue strips excised from those with diabetes. Furthermore, relaxation responses elicited by pinacidil and levcromakalim were not affected by charybdotoxin or 4-aminopyridine but were completely reversed by KCl or tetraethylammonium chloride. CONCLUSIONS: These data indicate that the adenosine triphosphate sensitive K channel subtype is likely to have an important role in the relaxation of isolated corporeal tissue strips and, moreover, they are the molecular target for the K channel modulators/openers levcromakalim and pinacidil. Such observations are consistent with the supposition that alterations in the structure/function/activity of these potassium channels may underlie at least some aspects of observed diabetes related differences in tissue sensitivity to K channel modulators.
机译：目的：人的身体平滑肌的持续收缩取决于通过电压门控钙通道的连续跨膜钙通量。钾离子通道调节了身体的平滑肌膜电位，从而最终影响跨膜钙通量。因此，我们表征了由K通道调节剂pinacidil和levcromakalim引起的对人孤立的人体组织条带的松弛反应。我们还评估了与糖尿病的存在相关的三磷酸腺苷敏感的K通道药理学/功能可能发生改变的可能性。材料与方法：调查了57例具有器质性勃起功能障碍的男性患者的215条分离的人体有形组织带。吡那地尔和左旋马卡林在等效去氧肾上腺素预收缩（约占最大量的75％）的分离的有孔组织条上，以稳态浓度松弛曲线的一半对数增量构建累积浓度-响应曲线。使用细胞附着的全细胞膜片钳技术在新鲜分离的有孔平滑肌细胞上测量钾电流。结果：对于品尼地尔和左旋克罗卡林，观察到了浓度依赖性的苯肾上腺素预先收缩的有形组织条对格列本脲敏感的松弛反应。与这样的观察结果一致，在新鲜分离的心肌细胞上的电生理记录表明，吡那地尔（10毫克）和左克鲁马卡林（10毫克）引起全细胞钾电流，而该电流被格列本脲（10毫克）阻断。此外，统计分析表明，与未患有糖尿病的患者切除的有孔组织条带相比，未患糖尿病的患者去氧肾上腺素预收缩的有孔组织条带对这两种化合物的松弛更为敏感。此外，吡那地尔和左旋克马卡林引起的松弛反应不受甲藻毒素或4-氨基吡啶的影响，但被氯化钾或氯化四乙铵完全逆转。结论：这些数据表明，三磷酸腺苷敏感的K通道亚型可能在松弛分离的有组织组织条带中起重要作用，而且，它们是K通道调节剂/开放剂levcromakalim和pinacidil的分子靶标。此类观察与以下假设一致：这些钾通道的结构/功能/活性的改变可能是所观察到的糖尿病相关组织对K通道调节剂敏感性差异的至少某些方面的基础。

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