Estudio de la estructura y función de canales iónicos y su modulación por sustancias endógenas y exógenas
Este Grupo está enfocado en la fisiología del músculo liso vascular humano y ha trabajado en la caracterización de canales iónicos mediante la técnica de patch-clamp en células aisladas de vena safena, arteria mamaria y arteria umbilical humana (AUH). El objetivo de estas investigaciones es caracterizar la actividad de canales iónicos que regulan la concentración de Ca2+ en las células de músculo liso de la AUH y determinar su rol en los mecanismos de contracción y relajación de la arteria. Por otro lado se ha comenzado a desarrollar nuevas líneas de investigación dirigidas al estudio de los mecanismos de acción de principios activos y sustancias endógenas que afectan al funcionamiento de distintos tipos de canales iónicos. Para potenciar este nuevo enfoque hemos incorporado nuevas metodologías tales como medida de corriente de canales expresados en un sistema de expresión heterólogo, modelado molecular y docking. Se han establecido convenios y colaboraciones con: Instituto Interdisciplinario de Neurociencias de Valparaíso, Chile (Dr. Ramón Latorre y el Dr. Carlos González) Servicio de Tocoginecología del Hospital Ricardo Gutiérrez de la ciudad de La Plata, estudiar la posible asociación entre patologías maternas que pueden afectar los vasos sanguíneos y alteraciones estructurales y funcionales de los vasos del cordón umbilical y su efecto sobre l morbi-mortalidad perinatal.
  1. An allosteric gating model recapitulates the biophysical properties of IK,L expressed in mouse vestibular Type I hair cells. Spaiardi P, Tavazzani E, Manca M, Milesi V, Russo G, Prigioni I, Marcotti W, Magistretti J, Masetto S. J Physiol. 2017 Sep 1. doi: 10.1113/JP274202. PMID: 28862328
  2. Diphenhydramine inhibits voltage-gated proton channels (Hv1) and induces acidification in leukemic Jurkat T cells- New insights into the pro-apoptotic effects of antihistaminic drugs. Asuaje A, Martín P, Enrique N, Díaz Zegarra LA, Smaldini P, Docena G, Milesi V. Channels (Austin). 2017 May 17:0. doi: 10.1080/19336950.2017.1331799. PMID: 28514187
  3. Dynamic regulation of extracellular ATP in Escherichia coli. Alvarez CL, Corradi G, Lauri N, Marginedas-Freixa I, Leal Denis MF, Enrique N, Mate SM, Milesi V, Ostuni MA, Herlax V, Schwarzbaum PJ. Biochem J. 2017 Apr 4;474(8):1395-1416. doi: 10.1042/BCJ20160879. PMID: 28246335
  4. The inhibition of voltage-gated H+ channel (HVCN1) induces acidification of leukemic Jurkat T cells promoting cell death by apoptosis. Asuaje A, Smaldini P, Martín P, Enrique N, Orlowski A, Aiello EA, Gonzalez León C, Docena G, Milesi V. Pflugers Arch. 2017 Feb;469(2):251-261. doi: 10.1007/s00424-016-1928-0. Epub 2016 Dec 24. PMID: 28013412
  5. Arachidonic acid activation of BKCa (Slo1) channels associated to the β1-subunit in human vascular smooth muscle cells. Martín P, Moncada M, Enrique N, Asuaje A, Valdez Capuccino JM, Gonzalez C, Milesi V. Pflugers Arch. 2014 Sep;466(9):1779-92. doi: 10.1007/s00424-013-1422-x. Epub 2013 Dec 28. PMID: 24375290
  6. Diversity of potassium channels in human umbilical artery smooth muscle cells: a review of their roles in human umbilical artery contraction. Martín P, Rebolledo A, Palomo AR, Moncada M, Piccinini L, Milesi V. Reprod Sci. 2014 Apr;21(4):432-41. doi: 10.1177/1933719113504468. Epub 2013 Sep 30. Review. PMID: 24084522
  7. A BK (Slo1) channel journey from molecule to physiology. Contreras GF, Castillo K, Enrique N, Carrasquel-Ursulaez W, Castillo JP, Milesi V, Neely A, Alvarez O, Ferreira G, González C, Latorre R. Channels (Austin). 2013 Nov-Dec;7(6):442-58. doi: 10.4161/chan.26242. Epub 2013 Sep 11. Review.PMID: 24025517
  8. Human umbilical artery smooth muscle exhibits a 2-APB-sensitive capacitative contractile response evoked by vasoactive substances and expresses mRNAs for STIM, Orai and TRPC channels. Roldán Palomo AR, Martín P, Rebolledo A, Enrique N, Flores LE, Milesi V. Biocell. 2012 Aug;36(2):73-81. PMID: 23185782
  9. Bupivacaine inhibits large conductance, voltage- and Ca2+- activated K+ channels in human umbilical artery smooth muscle cells. Martín P, Enrique N, Palomo AR, Rebolledo A, Milesi V. Channels (Austin). 2012 May-Jun;6(3):174-80. doi: 10.4161/chan.20362. PMID: 22688134
  10. Extracellular ATP induces fast and transient non-selective cationic currents and cytosolic Ca2+ changes in human umbilical artery smooth muscle cells. Enrique N, Rebolledo A, Martín P, Roldán Palomo AR, Tanzi F, Milesi V.
  11. Purinergic Signal. 2012 Jun;8(2):199-206. doi: 10.1007/s11302-011-9264-5. Epub 2011 Oct 4. PMID: 21969137
  12. Risperidone inhibits contractions induced by serotonin and histamine and reduces K+ currents in smooth muscle of human umbilical artery. Iveli MF, Rebolledo A, Martín P, Enrique N, Roldán Palomo AR, Rimorini L, Salemme S, Milesi V. Reprod Sci. 2010 Sep;17(9):854-60. doi: 10.1177/1933719110372420. PMID: 20601536
  13. Genistein effects on Ca2+ handling in human umbilical artery: inhibition of sarcoplasmic reticulum Ca2+ release and of voltage-operated Ca2+ channels. Speroni F, Rebolledo A, Salemme S, Roldán-Palomo R, Rimorini L, Añón MC, Spinillo A, Tanzi F, Milesi V. J PhysiolBiochem. 2009 Jun;65(2):113-24. PMID: 19886390
  14. Arginine-rich peptides destabilize the plasma membrane, consistent with a pore formation translocation mechanism of cell-penetrating peptides. Herce HD, Garcia AE, Litt J, Kane RS, Martin P, Enrique N, Rebolledo A, Milesi V. Biophys J. 2009 Oct 7;97(7):1917-25. doi: 10.1016/j.bpj.2009.05.066. PMID: 19804722
  15. Cardiac microvascular endothelial cells express a functional Ca+ -sensing receptor. Berra Romani R, Raqeeb A, Laforenza U, Scaffino MF, Moccia F, Avelino-Cruz JE, Oldani A, Coltrini D, Milesi V, Taglietti V, Tanzi F. J Vasc Res. 2009;46(1):73-82. doi: 10.1159/000140677. PMID: 18577871
  16. Genistein inhibits contractile force, intracellular Ca2+ increase and Ca2+ oscillations induced by serotonin in rat aortic smooth muscle. Speroni F, Rebolledo A, Salemme S, Añón MC, Tanzi F, Milesi V. J PhysiolBiochem. 2007 Jun;63(2):143-51. PMID: 17933388
  17. L, P-/Q- and T-type Ca2+ channels in smooth muscle cells from human umbilical artery. Salemme S, Rebolledo A, Speroni F, Petruccelli S, Milesi V. Cell PhysiolBiochem. 2007;20(1-4):55-64. PMID: 17595515
  18. Effects of light ethanol consumption during pregnancy: increased frequency of minor anomalies in the newborn and altered contractility of umbilical cord artery. Iveli MF, Morales S, Rebolledo A, Savietto V, Salemme S, Apezteguía M, Cecotti N, Drut R, Milesi V. Pediatr Res. 2007 Apr;61(4):456-61. PMID: 17515871
  19. The Na+/Ca2+ exchanger is active and working in the reverse mode in human umbilical artery smooth muscle cells. Rebolledo A, Speroni F, Raingo J, Salemme SV, Tanzi F, Munin V, Añón MC, Milesi V. BiochemBiophys Res Commun. 2006 Jan 20;339(3):840-5. PMID: 16325771
  20. pH effects on high conductance Ca2+-activated K+ channels (BK(Ca)) in human internal mammary artery smooth muscle cells. Raingo J, Rebolledo A, Grassi de Gende AO, Sanz N, Tommasi J, Milesi V. Life Sci. 2005 Sep 2;77(16):1993-2003. PMID: 15927206
  21. Non-selective cationic channels (NSCC) in smooth muscle cells from human umbilical arteries. Raingo J, Rebolledo A, Iveli F, Grassi de Gende AO, Milesi V. Placenta. 2004 Sep-Oct;25(8-9):723-9. PMID: 15450390
  22. Cardiac and vascular effects of diltiazem, dobutamine and amrinone, drugs used after myocardial revascularization. Gómez-Alvis A, Rebolledo A, Milesi V, Raingo J, Sanz N, Tommasi J, Drago A, Rinaldi G, Grassi A. Braz J Med Biol Res. 2004 Jun;37(6):893-900. Epub 2004 May 27.PMID: 15264033
  23. Potassium channels in human umbilical artery cells. Milesi V, Raingo J, Rebolledo A, Grassi de Gende AO. J SocGynecolInvestig. 2003 Sep;10(6):339-46.PMID: 12969776
  24. Insulin preincubation effects on rat vessel contractile responses: role of the sarcoplasmic reticulum. Rebolledo A, Milesi V, Raingo J, Gómez Alvis A, Rinaldi GJ, Grassi de Gende AO. Endothelium. 2001;8(4):277-82. PMID: 11824480
  25. Insulin preincubation effects on rat vessel contractile responses: role of the endothelium. Rebolledo A, Rinaldi GJ, Milesi V, Gómez Alvis A, Grassi de Gende AO. Endothelium. 2001;8(4):269-76. PMID: 11824479
  26. Influence of calcitonin gene-related peptide release on pH-induced mechanical depression in rat atria. Alvis AG, Milesi V, Rebolledo A, Raingo J, Grassi de Gende AO. JpnHeart J. 2001 Jul;42(4):507-17. PMID: 11693286
  27. Structural and functional aspects of the human saphenous vein used as aorto-coronary graft in myocardial revascularization Milesi V, Rebolledo A, Gómez Alvis A, Sanz N, Tommasi J, Drago A, Raingo J, Rinaldi GJ, Grassi de Gende AO. Medicina (B Aires). 2001;61(4):481-90. Review.PMID: 11563178
  28. Voltage-activated sodium current is inhibited by capsaicin in rat atrial myocytes. Milesi V, Rebolledo A, Alvis AG, Raingo J, Grassi de Gende AO. BiochemBiophys Res Commun. 2001 Apr 13;282(4):965-70. PMID: 11352646
  29. Short-term streptozotocin-induced diabetes induces blood pressure decrease associated with reduced aortic (45)Ca(2+) uptake and selective depression of the sustained noradrenergic contraction. Rebolledo A, Ayala-Paredes F, Milesi V, Grassi AO, Rinaldi GJ. Diabetes Metab. 2001 Feb;27(1):40-8. PMID: 11240445
  30. The antineoplastic agent paclitaxel (Taxol) increases contractile activity in human saphenous veins and human mammary arteries. Gómez-Alvis A, Rinaldi G, Rebolledo A, Milesi V, Sanz N, Tommasi J, Grassi de Gende A. Cancer Invest. 2000;18(4):327-35. PMID: 10808368
  31. Role of insulin preincubation in the contractile reactivity of rat aortic rings. Rebolledo A, Milesi V, Alvis AG, Rinaldi GJ, Grassi de Gende AO. Can J PhysiolPharmacol. 1998 Dec;76(12):1066-71. PMID: 10326827
  32. Role of a Ca2+-activated K+ current in the maintenance of resting membrane potential of isolated, human, saphenous vein smooth muscle cells. Milesi V, Aiello EA, Rebolledo A, GomezAlvis A, Grassi de Gende AO. Pflugers Arch. 1999 Feb;437(3):455-61. PMID: 9914403
  33. Mechanical properties of human saphenous veins from normotensive and hypertensive patients. Milesi V, Rebolledo A, Ayala Paredes F, Sanz N, Tommasi J, Rinaldi GJ, Grassi AO.Ann Thorac Surg. 1998 Aug;66(2):455-61. PMID: 9725384
  34. Chronotropic, inotropic and lusitropic effects of capsaicin on isolated rat atria. GomezAlvis A, Quiroga P, Rebolledo A, Milesi V, Mandrile E, Grassi A. ActaPhysiolPharmacolTherLatinoam. 1998;48(2):65-72. PMID: 9695877
  35. Chronotropic, inotropic and lusitropic effects of capsaicin on isolated rat atria. GomeEffect of insulin on contractile response and calcium binding in rat aorta Rebolledo A, Milesi V, Rinaldi G, Grassi A. Medicina (B Aires). 1996;56(6):671-8. PMID: 9284570
  36. Chronotropic, inotropic and lusitropic effects of capsaicin on isolated rat atria. GomeInsulin, vascular reactivity and hypertension Rebolledo A, Milesi V, Rinaldi G, Grassi A. Medicina (B Aires). 1996;56(5 Pt 1):518-26. Review. PMID: 9239888