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Effects of ethanol on the tonicity of corporal tissue and the intracellular Ca^2＋ concentration of human corporal smooth muscle cells

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Asian Journal of Andrology 2010年第6期12卷 890-898页

作者： Sung Chul Kam mee ree chae Ji Young Kim Seol Ho Choo Deok Hyun Han Sung Won Lee Department of Urology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul 135-710 Korea

Heavy alcohol consumption is associated with an increased risk of erectile dysfunction （ED）; however, the acute effects of ethanol （EtOH） on penile tissue are not fully understood. We sought to investigate the effects of EtOH on corporal tissue tonicity, as well as the intracellular Ca^2＋ concentration （[Ca^2＋]i） and potassium channel activity of corporal smooth muscle. Strips of corpus cavernosum （CC） from rabbits were mounted in organ baths for isometric tension studies. Electrical field stimulation （EFS） was applied to strips precontracted with 10 μmol L^-1 phenylephrine as a control. EtOH was then added to the organ bath and incubated before EFS. The [Ca^2＋]i levels were monitored by the ratio of fura-2 fluorescence intensities using the fura-2 loading method. Single-channel and whole-cell currents were recorded by the conventional patch-clamp technique in short-term cultured smooth muscle cells from human CC tissue. The corpus cavernosal relaxant response of EFS was decreased in proportion to the concentration of EtOH. EtOH induced a sustained increase in [Ca^2＋]i in a dose-dependent manner, Extracellular application of EtOH significantly increased whole-cell K^＋ currents in a concentration-dependent manner （P 〈 0.05）. EtOH also increased the open probability in cell-attached patches; however, in inside-out patches, the application of EtOH to the intracellular aspect of the patches induced slight inhibition of Ca^2＋-activated potassium channel （KCa） activity. EtOH caused a dose-dependent increase in cavemosal tension by alterations to [Ca^2＋]i. Although EtOH did not affect KCa channels directly, it increased the channel activity by increasing [Ca^2＋]i. The increased corpus cavemosal tone caused by EtOH might be one of the mechanisms of ED after heavy drinking.

关键词： alcohol Ca^2+-activated potassium channel corporal smooth muscle penile erection

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Effects of Ginkgo biloba extracts with mirodenafil on the relaxation of corpus cavernosal smooth muscle and the potassium channel activity of corporal smooth muscle cells

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Asian Journal of Andrology 2011年第5期13卷 742-746页

作者： Jung Jun Kim Deok Hyun Han Soo Hyun Lim Tae Hun Kim mee ree chae Kyung Jin Chung Sung Chul Kam Ju-Hong Jeon Jong Kwan Parks Sung Won Lee Department of Urology Samsung Medical Center Sungkyunkwan University School of Medicine Seou1135-710 Korea Department of Urology Gachon University Gil Hospital Incheon 405-760 Korea Department of Urology Gyeengsang National University College of Medicine Gyeongsangnam-do 660-702 Korea Department of Physiology and Biophysics Seeul National University College of Medicine Seeul 110-799 Korea Department of Urology Medical School Chonbuk National University and Institute for Medical Sciences Chonbuk National University and Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University Hospital Jeonju-si 561-712 Korea

In this study, we investigated the effects of a combination of Ginkgo biloba extracts （GBE） and phosphodiesterase type 5 （PDE-5） inhibitors on the muscular tone of the corpus cavernosum and potassium channel activity of corporal smooth muscle cells. Strips of corpus cavernosum from male New Zealand white rabbits were mounted in organ baths for isometric tension studies. After contraction with 1 × 10^-5 mol I^-1 norepinephrine, GBE （0.01-1 mg ml^-1） and mirodenafil （0.01-100 nmol I^-1） were added together into the organ bath. In electrophysiological studies, whole-cell currents were recorded by the conventional patch-clamp technique in cultured smooth muscle cells of the human corpus cavernosum. The corpus cavemosum was relaxed in response to GBE in a dose-dependent manner （from 0.64%±8.35% at 0.01 mg ml^-1 to 52.28%±11.42% at 1 mg ml^-1）. After pre-treatment with 0.03 mg ml^-1 of GBE, the relaxant effects of mirodenafil were increased at all concentrations, After tetraethylammonium （TEA）（1 mmol I^-1） administration, the increased effects were inhibited （P〈0.01）. Extracellular administration of GBE increased the whole-cell K^＋ outward currents in a dose-dependent fashion. The increase of the outward current was inhibited by I mmol 1-1 TEA. These results suggest that GBE could increase the relaxant potency of mirodenafil even at a minimally effective dose. The K＋ flow through potassium channels might be one of the mechanisms involved in this synergistic relaxation.

关键词： calcium-activated potassium channels erectile dysfunction Ginkgo biloba phosphodiesterase inhibitors smooth muscles

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