Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces the change of calcium mobilization via TRPC ion channels in cultured human corporal smooth muscle cells.
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 (F(340/380)) 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 microM) induced a statistically significant increase in F(340/380) to 119.9+/-3.9% of initial control (n=6) in corporal smooth muscle cells. The addition of 20 microM 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, TRPC6alpha. 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.
So
I
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Department of Physiology and Biophysics, Seoul National University College of Medicine, Seoul, Republic of Korea.
Chae
M R
MR
Kim
S J
SJ
Lee
S W
SW
D017398:Alternative Splicing; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D002478:Cells, Cultured; D004553:Electric Conductivity; D004594:Electrophysiology; D007172:Erectile Dysfunction / Q000209:etiology; D005456:Fluorescent Dyes; D016257:Fura-2; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications; D008077:Lipoproteins, LDL / Q000737:chemistry; D008244:Lysophosphatidylcholines / Q000032:analysis / Q000494:pharmacology*; D008297:Male; D008345:Manganese / Q000494:pharmacology; D009130:Muscle, Smooth / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010413:Penis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050052:TRPC Cation Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000074287:TRPC6 Cation Channel
D005456:Fluorescent Dyes; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; C099252:oxidized low density lipoprotein; D008345:Manganese; D002118:Calcium; D016257:Fura-2