FACULTY
| Virginijus Valiunas Research Associate Professor Ph.D. Kaunas Medical Academy (Lithuania), 1992 Basic Science Tower, T-5, Room 190 Stony Brook University Stony Brook, NY, 11794-8661 Phone: (631) 444-3474 Email: Virginijus.Valiunas@stonybrook.edu |
| Research | Cell to Cell Communication: Gap Junction Channels and Hemichannels. Our research interest is to study cell to cell communication that is mediated by gap junctions. The major emphases are determining biophysical properties, gating, regulation and perm-selectivity of gap junction channels and hemichannels that are formed by connexin proteins. We use simultaneously electrophysiological (single and double voltage patch clamp) and fluorescent-imaging methods to study electrical and metabolic coupling in cells expressing wild-type and disease associated mutant connexins. The goals of the current research effort are to investigate the role of connexin perm-selectivity qualitatively and quantitatively. This includes studying the permeability to known signaling molecules, such as cyclic nucleotides in normal physiology and in human hereditary diseases like oculodentodigital dysplasia and cardiac arrhythmias.
Our research expertise includes demonstrating that small interfering RNA can pass via gap junctions and silence the expression of target proteins in coupled neighboring cells. We have also developed a novel method for monitoring the permeability of the second messenger cAMP by using a cyclic nucleotide modulated channel gene as a reporter. Our work has clearly established that Cx40 and Cx43 have profoundly different perm-selectivity properties to specific molecules, including cAMP. Furthermore, we demonstrated that human mesenchymal stem cells (hMSCs) express Cx43 and Cx40 and also make functional gap junction channels with cardiac myocytes. We used hMSCs to carry pacemaker genes to isolated canine ventricular myocytes, demonstrating that the two cell unit can function as a biological pacemaker. |
| Selected Publications | Valiunas V. Cyclic nucleotide permeability through unopposed connexin hemichannels. Front.Pharmacol. 2013 June. Mayan MD, Carpintero-Fernandez P, Gago-Fuentes R, Martinez-de-Ilarduya O, Wang ZH, Valiunas V, Brink P, Blanco FJ. Human articular chondrocytes express multiple gap junction proteins: differential expression of connexins in normal and osteoarthritic cartilage. Am J of Pathol. 2013 Apr; 182(4):1337-46. Clausen C, Valiunas V, Brink PR, Cohen IS. MATLAB implementation of a dynamic clamp with bandwidth of >125 kHz capable of generating I (Na) at 37 °C. Pflugers Arch. 2013 Apr;465(4):497-507 Brink PR, Valiunas V, Gordon C, Rosen MR, Cohen IS. Can gap junctions deliver? Biochim Biophys Acta. 2012 Aug; 1818(8):2076-8. Mese G, Sellitto C, Li L, Wang HZ, Valiunas V, Richard G, Brink PR, White TW. The Cx26-G45E mutation displays increased hemichannel activity in a mouse model of the lethal form of keratitis-ichthyosis-deafness syndrome. Mol Biol Cell. 2011 Dec;22(24):4776-86. Jia Z, Valiunas V, Lu Z, Bien H, Liu H, Wang HZ, Rosati B, Brink PR, Cohen IS, Entcheva E. Stimulating cardiac muscle by light: cardiac optogenetics by cell delivery. Circ Arrhythm Electrophysiol. 2011 Oct;4(5):753-60. Kanaporis G, Brink PR, Valiunas V. Gap Junction Permeability: selectivity for anionic and cationic probes. Am J Physiol Cell Physiol. 2011 Mar;300(3):C600-9 Valiunas V, G. Kanaporis G, Valiuniene L, Gordon C, Wang HZ, Li L,Robinson RB, Rosen MR, Cohen IS, Brink PR. Coupling an HCN2 expressing cell to a myocyte creates a two cell pacing unit. J Physiol. 2009;587(Pt 21):5211-26. Mese G, Valiunas V, Brink P, White TW. Connexin26 deafness associated mutations show altered permeability to large cationic molecules. Am J Physiol Cell Physiol. 2008 Oct; 295(4):C996-74. Kanaporis G, Mese G, Valiuniene L, White TW, Brink PR, and Valiunas V. Gap junction channels exhibit connexin-specific permeability to cyclic nucleotides. J Gen Phys, 2008; Apr;131(4):293-305. Yum SW, Zhang J, Valiunas V, Kanaporis G, Brink PR, White TW, Sherer SS. Human connexin26 and connexin30 form functional heteromeric and heterotypic channels. Am J Physiol Cell Physiol, 2007; 293(3): C1032-48. Vogel R, Valiunas V, Weingart R. Subconductance states of Cx30 gap junction channels: data from transfected HeLa cells versus data from a mathematical model. Biophys J , 2006 Sep 15;91(6):2337-48. Brink PR, Valiunas V, Wang HZ, Zhao W, Davies K and Christ GJ. Experimental diabetes alters Connexin43-derived gap junction permeability in short term cultures of rat corporal vascular smooth muscle cells. J Urol. 2006; 175(1): 381-6. Ramanan SV, Valiunas V, Brink PR. Non-stationary fluctuations analysis of macroscopic gap junction channel records. J Membr Biol. 2005; 205: 81-88. Valiunas V, Polosina YY, Miller H, Potapova IA, Valiuniene L, Doronin S, Mathias RT, Robinson RB, Rosen MR, Cohen IS and Brink PR. Connexin-Specific Cell to Cell Transfer of Short Interfering RNA by Gap Junctions. J Physiol. 2005; 568.2:459-68. Valiunas V, Bechberger JF, Naus CG, Brink PR, Goldberg GS. Nontransformed cells can normalize gap junctional communication with transformed cells. Biochem Biophys Res Commun. 2005; 333(1): 174-9. Valiunas V, Mui R, McLachlan E, Valdimarsson G, Brink PR, White TW. Biophysical Characterization of Zebrafish Connexin35 Hemichannels. Am J Physiol. 2004 Dec, 287 (6): C1596-C1604. Potapova I, Plotnikov A, Lu Z, Danilo P, Valiunas V, Qu J, Doronin S, Zuckerman J, Shlapakova I, Gao J, Pan Z, Herron A, Robinson RB, Brink PR Rosen M, and Cohen IS. Human Mesenchymal Stem Cells as a Gene Delivery System to fabricate a Biological Pacemaker. Circ Res. 2004; 94(7):952-9. Valiunas V, Doronin S, Valiuniene L, Potapova I, Zuckerman J, Walcott B, Robinson RB, Rosen M, Brink PR and Cohen IS. Human Mesenchymal Stem Cells make Cardiac Connexins and form Functional Gap Junctions. J Physiol. 2004, 555.3:617- 626. Valiunas V, Beyer EC, Brink PR. Cardiac gap junction channels show quantitative differences in selectivity. Circ Res. 2002; 91(2):104-11. Polontchouk L, Valiunas V, Haefliger JA, Eppenberger H, Weingart R. Expression and regulation of connexins in cultured ventricular myocytes isolated from adult rat hearts. Pflugers Arch. 2002;443(5):676-89. Valiunas V. Biophysical properties of connexin45 gap junction hemichannels studied in vertebrate cells. J Gen Phys. 2002; Febr;147-164. Valiunas V, Gemel J, Brink PR, Beyer EC. Gap junction channels formed by coexpressed connexin40 and connexin43. Am J Physiol Heart Circ Physiol. 2001;281(4):H1675-89. Valiunas V, Weingart R. Cooperativity between mouse connexin30 gap junction channels. Pflügers Arch. 2001; 441 (6): 756-760. Valiunas V, Vogel R, Weingart R. The kinetics of gap junction currents are sensitive to the ionic composition of the pipette solution. Pflügers Arch. 2000; 440:835-842. Valiunas V, Weingart R. Electrical properties of gap junction hemichannels identified in transfected cells. Pflügers Arch. 2000; 440:366-379. Valiunas V, Weingart R, Brink PR. Formation of heterotypic gap junction channels by connexins Cx40 and Cx43. Circ Res. 2000; 86:e42-e49. Valiunas V, Manthey D, Vogel R, Willecke, Weingart R. Biophysical properties of gap junction channels formed by mouse connexin30 expressed in transfected human Hela cells. J Physiol. 1999;519(3):631-644. Valiunas V, Niessen H, Willecke K, Weingart R. Electrophysiological properties of gap junction channels in hepatocytes isolated from connexin32 deficient and wild type mice. Pflügers Arch. 1999; 437:846-856. Valiunas V, Bukauskas FF, Weingart R. Conductances and selective permeability of connexin 43 gap junction channels examined in neonatal rat heart cells. Circ Res.1997; 80:708-719. |
