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Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces the change of calcium mobilization via TRPC ion channels in cultured human corporal smooth muscle cells

Abstract

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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References

  1. Wei M, Macera CA, Davis DR . Total cholesterol and high density lipoprotein cholesterol as important predictors of erectile dysfunction. Am J Epidemiol 1994; 140: 930–937.

    CAS  Article  Google Scholar 

  2. Kim JH . Experimental hypercholesterolemia in rabbits induces cavernosal atherosclerosis with endothelial and smooth muscle cell dysfunction. J Urol 1994; 151: 198–205.

    CAS  Article  Google Scholar 

  3. Ahn TY et al. Enhanced contractility of rabbit corpus cavernosum smooth muscle by oxidized low density lipoproteins. Int J Impot Res 1999; 11: 9–14.

    CAS  Article  Google Scholar 

  4. Yesilli C, Yaman O, Anafarta K . Effect of experimental hypercholesterolemia on cavernosal structures. Urology 2001; 57: 1184–1188.

    CAS  Article  Google Scholar 

  5. Kugiyama K et al. Impairment of endothelium-dependent arterial relaxation by lysolecithin in modified low density lipoproteins. Nature 1990; 344: 160–169.

    CAS  Article  Google Scholar 

  6. Cox DA, Cohen ML . Effects of oxidized low-density lipoprotein on vascular contraction and relaxation: Clinical and pharmacological implications in atherosclerosis. Pharmacol Rev 1996; 48: 3–19.

    CAS  PubMed  Google Scholar 

  7. Kume N, Cybulsky MI, Gimbrone Jr MA . Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells. J Clin Invest 1992; 90: 1138–1144.

    CAS  Article  Google Scholar 

  8. Christ GJ . The penis as a vascular organ: the importance of corporal smooth muscle tone in the control of erection. Urol Clin North Am 1995; 22: 727–745.

    CAS  PubMed  Google Scholar 

  9. Kuriyama H, Kitamura K, Nabata H . Pharmacological and physiological significance of ion channels and factors that modulate them in vascular tissues. Pharmacol Rev 1995; 47: 387–573.

    CAS  PubMed  Google Scholar 

  10. Nelson MT et al. Relaxation of arterial smooth muscle by calcium sparks. Science 1995; 270: 633–637.

    CAS  Article  Google Scholar 

  11. Vennekens R et al. Current understanding of mammalian TRP homologues. Cell Calcium 2002; 31: 253–264.

    CAS  Article  Google Scholar 

  12. Lee YM et al. TRPC5 as a candidate for the nonselective cation channel activated by muscarinic stimulation in murine stomach. Am J Physiol Gastrointest Liver Physiol 2003; 284: G604–G616.

    CAS  Article  Google Scholar 

  13. SO I et al. Molecular basis and characteristics of KATP channel in human corporal smooth muscle cells. Int J Impot Res 2003; 15: 258–266.

    Article  Google Scholar 

  14. Merritt JE, Jacob R, Hallam TJ . Use of manganese to discriminate between calcium influx and mobilization from internal stores in stimulated human neutrophils. J Biol Chem 1989; 264: 1522–1527.

    CAS  PubMed  Google Scholar 

  15. Inoue R, Kuriyama H . Dual regulation of cation-selective channels by muscarinic and α1-adrenergic receptors in the rabbit portal vein. J Physiol 1993; 465: 427–448.

    CAS  Article  Google Scholar 

  16. Helliwell RM, Large WA . Dual effect of external Ca2+ on noradrenaline-activated cation current in rabbit portal vein smooth muscle cells. J Physiol 1996; 492: 75–88.

    CAS  Article  Google Scholar 

  17. Inoue R et al. The transient receptor potential protein homologue TRP6 is the essential component of vascular α1-adrenoceptor-activated Ca2+-permeable cation channel. Circ Res 2001; 88: 325–332.

    CAS  Article  Google Scholar 

  18. Zhang L, Saffen D . Muscarinic acetylcholine receptor regulation of TRPC6 Ca2+ channel isoforms. J Biol Chem 2001; 276: 13331–13339.

    CAS  Article  Google Scholar 

  19. Terasawa K et al. Nonselective cation currents regulate membrane potential of rabbit coronary arterial cell: modulation by lysophosphatidylcholine. Circulation 2002; 106: 3111–3119.

    Article  Google Scholar 

  20. Wamhoff BR, Dixon JL, Sturek M . Atorvastatin treatment prevents alterations in coronary smooth muscle nuclear Ca2+ signaling in diabetic dyslipidemia. J Vasc Res 2002; 39: 208–220.

    CAS  Article  Google Scholar 

  21. Andersson KE . Erectile physiological and pathophysiological pathways involved in erectile dysfunction. J Urol 2003; 170: S6–S14.

    Article  Google Scholar 

  22. Kim SJ et al. Ca2+ influx through carbachol-activated non-selective cation channels in guinea-pig gastric myocytes. J Physiol 1998; 513: 749–760.

    CAS  Article  Google Scholar 

  23. Montell C, Birnbaumer L, Flockerzi V . The TRP channels, a remarkably functional family. Cell 2002; 108: 595–598.

    CAS  Article  Google Scholar 

  24. Vazquez G et al. The mammalian TRPC cation channels. Biochim Biophys Acta 2004; 1742: 21–36.

    CAS  Article  Google Scholar 

  25. Kabarowski JH et al. Lysophosphatidylcholine as a ligand for the immunoregulatory receptor G2A. Science 2001; 293: 702–705.

    CAS  Article  Google Scholar 

  26. Zhu K et al. Sphingosylphosphorylcholine and lysophosphatidylcholine are ligands for the G protein-coupled receptor GPR4. J Biol Chem 2001; 276: 41325–41335.

    CAS  Article  Google Scholar 

  27. Jung S, Strotmann R, Schultz G, Plant TD . TRPC6 is a candidate channel involved in receptor-stimulated cation currents in A7r5 smooth muscle cells. Am J Physiol Cell Physiol 2002; 282: C347–C359.

    CAS  Article  Google Scholar 

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Acknowledgements

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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Correspondence to S W Lee.

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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

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Keywords

  • erectile dysfunction
  • lysophosphatidylcholine
  • transient receptor potential channel
  • corporal smooth muscle cells

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