Deok Hyun Han1, Mee Ree Chae1, Jae Hun Jung1, Insuk So2, Jong Kwan Park3, Sung Won Lee4. 1. Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Irwon-dong, Gangnam-gu, Seoul 135-710, South Korea. 2. Department of Physiology and Biophysics, Seoul National University College of Medicine, 28 Yeongeon-dong, Jongno-gu, Seoul 110-799, South Korea. 3. Department of Urology, Chonbuk National University Medical School and Chonbuk National University Institute for Medical Sciences and Research Institute of Clinical Medicine of Chonbuk National University Hospital, 2-20, Keum-Am-Dong-San, Chonju 561-712, South Korea. 4. Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Irwon-dong, Gangnam-gu, Seoul 135-710, South Korea;. Electronic address: drswlee@smc.samsung.co.kr.
Abstract
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-BK(Ca) 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 BK(Ca) and K(ATP) channels by testosterone. Results. Testosterone (200 nM) significantly increased the single-channel activity of calcium-activated potassium (BK(Ca)) 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 BK(Ca) 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 BK(Ca) channel was activated to a significantly higher degree than was induced by testosterone alone. CONCLUSIONS: The results of patch-clamp studies provided direct molecular evidence that testosterone stimulates the activity of BK(Ca) 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.
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-BK(Ca) 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 BK(Ca) and K(ATP) channels by testosterone. Results. Testosterone (200 nM) significantly increased the single-channel activity of calcium-activated potassium (BK(Ca)) 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 BK(Ca) 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 BK(Ca) channel was activated to a significantly higher degree than was induced by testosterone alone. CONCLUSIONS: The results of patch-clamp studies provided direct molecular evidence that testosterone stimulates the activity of BK(Ca) 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.
Authors: Viju Deenadayalu; Yashoda Puttabyatappa; Alexander T Liu; John N Stallone; Richard E White Journal: Am J Physiol Heart Circ Physiol Date: 2011-11-11 Impact factor: 4.733
Authors: Biljana Musicki; Anthony J Bella; Trinity J Bivalacqua; Kelvin P Davies; Michael E DiSanto; Nestor F Gonzalez-Cadavid; Johanna L Hannan; Noel N Kim; Carol A Podlasek; Christopher J Wingard; Arthur L Burnett Journal: J Sex Med Date: 2015-12-08 Impact factor: 3.802