Hypercholesterolemia is a major risk factor for erectile dysfunction. To understand the mechanism(s) of hypercholesterolemia-induced erectile dysfunction, we studied the effect of lysophosphatidylcholine (LPC) on the membrane conductance of corporal smooth muscle cells. We used cultured human corporal smooth muscle cells. The intracelluar Ca2+ concentration ([Ca2+]i) and the influx of divalent cation was monitored by the ratio of fura-2 fluorescence (F340/380) and by the Mn2+-induced quenching rate of fura-2, respectively. The LPC-induced membrane current was characterized by the whole-cell patch-clamp technique and the molecular identity of suspected channels was probed by RT-PCR. LPC (20 μM) induced a statistically significant increase in F340/380 to 119.9±3.9% of initial control (n=6) in corporal smooth muscle cells. The addition of 20 μM LPC accelerated the quenching rate of F360 by 59.5±11.8% (n=5). LPC activated nonselective cationic current (ILPC), similar to the known effects of phenylephrine in corporal myocytes. The size of ILPC at −60 mV was −55.3±6.3 pA (n=8). The transcript of transient receptor potential channel 6 (TRPC6) was detected in human corporal myocytes. We also found one splicing variant of TRPC6, TRPC6α. In conclusion, the present study suggests that the LPC, a major component of oxidized low-density lipoprotiens, increases calcium in corporal smooth muscle cells probably through activation of a TRPC6 channel and the increased [Ca2+]i by LPC via TRP channels is one of mechanisms for hypercholesterolemia-induced erectile dysfunction.
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This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (No.: 01-PJ1-PG3-20500-0053).
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So, I., Chae, M., Kim, S. et al. Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces the change of calcium mobilization via TRPC ion channels in cultured human corporal smooth muscle cells. Int J Impot Res 17, 475–483 (2005). https://doi.org/10.1038/sj.ijir.3901356
- erectile dysfunction
- transient receptor potential channel
- corporal smooth muscle cells
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