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Effect of testosterone on potassium channel opening in human corporal smooth muscle cells
Deok Hyun Han1, Mee Ree Chae1, Jae Hun Jung1
1Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Irwon-dong, Gangnam-gu, Seoul 135-710, South Korea.
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.
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