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 mu M) 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 mu M LPC accelerated the quenching rate of F-360 by 59.5 +/- 11.8% (n=5). LPC activated nonselective cationic current (I-LPC), similar to the known effects of phenylephrine in corporal myocytes. The size of I-LPC 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, TRPC6 alpha. 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.