Effect of testosterone on potassium channel opening in human corporal smooth muscle cells
Effect of testosterone on potassium channel opening in human corporal smooth muscle cells
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DOI：
10.1111/j.1743-6109.2007.00732.x
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发表时间：
2008-04-01
影响因子：
3.5
通讯作者：
Lee, Sung Won
中科院分区：
文献类型：
--
作者：
Han, Deok Hyun;Chae, Mee Ree;Lee, Sung Won
导论.在人类中，睾酮在性功能中的作用，包括性欲，夜间阴茎勃起和射精量，已经相对较好地建立起来。然而，睾酮对人类阴茎内结构的影响仍然存在争议。我们评估了睾酮对人阴茎海绵体平滑肌细胞钾通道的直接影响，试图从细胞和分子水平了解睾酮诱导阴茎海绵体平滑肌细胞松弛的内在机制。我们用培养的人阴茎海绵体平滑肌细胞进行了电生理学研究。我们通过测定全细胞电流和单通道活性来评估睾酮对钾通道-BKCa和K-ATP通道的影响。对于电生理记录，采用全细胞和细胞贴附配置膜片钳技术。睾酮对BKCa和K-ATP通道全细胞电流和通道活性的影响。替吉奥（200 nM）显著增加钙激活钾（BKCa）通道的单通道活性和全细胞K+电流443.4 +/- 83.4%（+60 mV; N = 11，P < 0.05），这种作用被BKCa通道阻断剂四乙基铵（TEA）（1 mM）消除。K-ATP通道的全细胞内向K+电流也增加了226.5 ± 49.3%（-100 mV; N = 7，P < 0.05）。在vardenafil（10 nM）和睾酮（200 nM）的组合存在下，BKCa通道的激活程度显著高于睾酮单独诱导的程度。膜片钳研究的结果提供了直接的分子证据，表明睾酮刺激BKCa通道和K-ATP通道的活性。对睾酮受体激活与钾通道刺激的信号传导机制的理解将为我们深入了解睾酮血管舒张作用的细胞过程提供帮助。Han DH，Chae MR，Jung JH，So I，Park JK，and Lee SW.睾酮对人身体平滑肌细胞钾通道开放的影响。J Sex Med 2008;5：822-832。
Introduction. In humans, the role of testosterone in sexual functions, including sexual desire, nocturnal penile erections, and ejaculatory volume, has been relatively well established. However, the effects of testosterone on intrapenile structure in humans remains controversial.Aim. We assessed the direct effects of testosterone on potassium channels in human corporal smooth muscle cells, in an effort to understand the mechanisms inherent to the testosterone-induced relaxation of corporal smooth muscle cells at the cellular and molecular levels.Methods. We conducted electrophysiologic studies using cultured human corporal smooth muscle cells. We evaluated the effects of testosterone on potassium channels-BKCa and K-ATP channels-by determining the whole-cell currents and single-channel activities. For the electrophysiologic recordings, whole-cell and cell-attached configuration patch-clamp techniques were utilized.Main Outcome Measures. Changes in whole-cell currents and channel activities of BKCa and K-ATP channels by testosterone.Results. Testosterone (200 nM) significantly increased the single-channel activity of calcium-activated potassium (BKCa) channels and whole-cell K+ currents by 443.4 +/- 83.4% (at +60 mV; N = 11, P < 0.05), and this effect was abolished by tetraethylammonium (TEA) (1 mM), a BKCa channel blocker. The whole-cell inward K+ currents of the K-ATP channels were also increased by 226.5 +/- 49.3% (at -100 mV; N = 7, P < 0.05). In the presence of a combination of vardenafil (10 nM) and testosterone (200 nM), the BKCa channel was activated to a significantly higher degree than was induced by testosterone alone.The results of patch-clamp studies provided direct molecular evidence that testosterone stimulates the activity of BKCa channels and K-ATP channels. An understanding of the signaling mechanisms that couple testosterone receptor activation to potassium channel stimulation will provide us with an insight into the cellular processes underlying the vasorelaxant effects of testosterone. Han DH, Chae MR, Jung JH, So I, Park JK, and Lee SW. Effect of testosterone on potassium channel opening in human corporal smooth muscle cells. J Sex Med 2008;5:822-832.