Oleh M. Pochynyuk, Ph.D.
- Associate Professor
- Postdoctoral Fellow
- University of Texas Health Science Center, San Antonio, 2010
- Bogomoletz Institute of Physiology NAS, Kiev, Ukraine 2003
- Shevchenko Kiev State University, Ukraine 1999
Areas of Interest
Mechanisms of renal sodium reabsorption
Mechanisms of renal sodium reabsorption
The problem of elevated blood pressure is particularly important since more than 20% of all Americans suffer from high blood pressure. Kidneys play a well-recognized role in regulation of blood pressure by controlling water and sodium homeostasis. The fine-tuning of sodium balance occurs in the aldosterone-sensitive distal nephron (ASDN), including the connecting tubule and the collecting duct. Activity of the epithelial Na+ channel, ENaC, is limiting for discretionary sodium reabsorption across the ASDN. ENaC dysfunction results in various blood pressure disorders in humans, including hypertension associated with abnormal Na+ handling by the kidney. ENaC activity is known to be under negative feedback regulation by renin-angiotensin-aldosterone system (RAAS) with the mineralocorticoid, aldosterone stimulates channel activity to decrease sodium excretion in correction of falling circulating volume. Interestingly, signaling mechanisms intrinsic to the ASDN, including purinergic and bradykinin systems, play an important but as yet underappreciated role in regulation of sodium reabsorption and, thus, ENaC activity. This local control may be particularly important under conditions of elevated salt intake, which is common to the population in America, by limiting sodium reabsorption to avoid excessive sodium conservation and elevated blood pressure. Consistent with this, mice develop prominent salt-sensitive hypertension when these signaling cascades are compromised with genetic intervention. Our lab, by using a comprehensive experimental approach coupling direct measurements of channel activity with electrophysiology, biochemistry, molecular biology with genetic tools including specific knockout of membrane receptors, explores how these paracrine signalings complement RAAS to set ENaC activity in the mammalian ASDN.
ENaC is a highly Na+-selective, non-voltage gated, non-inactivated ion channel in the ENaC/Deg superfamily which also contains acid-sensing and mechano-sensitive Na+ channels found in neurons. The recently solved crystal structure of the ENaC/Deg channel, ASIC1A dramatically improves our understanding of ENaC structure/function relations. However, many fundamental properties of ENaC, including the mechanism of gating, remain elusive. Membrane phosphatidylinositides (such as PI(4,5)P2 and PI(3,4,5)P3) may directly interact with intracellular domains in the channel to modulate gating. We reconstitute ENaC in mammalian expression systems to define particular residues and motifs within the channel that are critical for channel gate and how interaction with these signaling molecules modulates channel activity.
- Hoover RS, Tomilin V, Hanson LN, Pochynyuk O, Ko B. (2015). PTH Modulation of NCC Activity Regulates TRPV5 Calcium Reabsorption. Am J Physiol Renal Physiol., Nov 25: [Epub ahead of print].
- Mamenko M, Dhande I, Tomilin V, Zaika O, Boukelmoune N, Zhu Y, Gonzalez-Garay ML, Pochynyuk O, Doris PA. (2015). Defective Store-Operated Calcium Entry Causes Partial Nephrogenic Diabetes Insipidus. J Am Soc Nephrol., Nov 16. pii: ASN.2014121200. [Epub ahead of print].
- Pavlov TS, Ilatovskaya DV, Palygin O, Levchenko V, Pochynyuk O, Staruschenko A. (2015). Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium. J Vis Exp., Sep 1;(103). doi: 10.3791/53035.
- Tomilin V, Mamenko M, Zaika O, Pochynyuk O. (2015). Role of renal TRP channels in physiology and pathology. Semin Immunopathol., Sep 18. [Epub ahead of print].
- Zaika O, Palygin O, Tomilin V, Mamenko M, Staruschenko A, Pochynyuk O. (2015). Insulin and IGF-1 activate Kir4.1/5.1 channels in cortical collecting duct principal cells to control basolateral membrane voltage. Am J Physiol Renal Physiol., Dec 2:ajprenal.00436.2015. doi: 10.1152/ajprenal.00436.2015. [Epub ahead of print].
- Berrout J, Mamenko M, Zaika OL, Chen L, Zang W, Pochynyuk O, and O’Neil RG. (2014). Emerging role of the calcium-activated, small conductance, SK3 K+ channel in distal tubule function: Regulation by TRPV4. PLoS ONE, 9:e95149.
- Berrout J, Mamenko M, Zaika OL, Pochynyuk O, and O’Neil R. (2014). Expression of the calcium-activated SK3 K+ channel in the mouse renal tubule. PLoS One, 9(4):e95149.
- Mamenko M, Zaika O, Boukelmoune N, O’Neil R, and Pochynyuk O. (2014). Deciphering physiological role of the mechanosensitive TRPV4 channel in the distal nephron. Am J Physiol Renal Physiol., Epub ahead of print.
- Mamenko M, Zaika O, Pochynyuk O. (2014). Direct regulation of ENaC by Bradykinin in the distal nephron. Implications for renal sodium handling. Curr Opin Nephrol Hypertens., 23: 122-129.
- Zaika O, Mamenko M, Boukelmoune N, and Pochynyuk O. (2014). IGF-1 and insulin exert opposite actions on ClC-K2 activity in the cortical collecting ducts. Am J Physiol Renal Physiol., Epub ahead of print.
- Kakoki M, Pochynyuk O, Hathaway CM, Tomita H, Hagaman JR, Kim H-S, Zaika OL, Mamenko M, Kayashima Y, Matsuki K, Hiller S, Li F, Xu L, Grant R, Bertorello AM, and Smithies O. (2013). Primary aldosteronism and impaired natriuresis in mice underexpressing TGFβ1. Proc Natl Acad Sci., U.S.A., 110(14):5600-5.
- Mamenko M, Zaika OL, Boukelmoune N, Berrout J, O’Neil RG, Pochynyuk O. (2013). Discrete control of TRPV4 channel function in the distal nephron by protein kinases A and C. J Biol Chem., 288:20306-14.
- Mamenko M, Zaika OL, O’Neil RG, and Pochynyuk O. (2013). Ca2+ imaging as a tool to assess TRP channel function in murine distal nephrons. “Ion Channels. Methods and Protocols, Second edition.” Methods Mol Biol., 998:371-84.
- Mamenko M, Zaika O, Prieto MC, Jensen VB, Doris PA, Navar LG, Pochynyuk O. (2013). Chronic Ang II infusion drives extensive aldosterone-independent ENaC activation. Hypertension, 62(6):1111-22.
- Mironova E, Bugay V, Pochynyuk O, Staruschenko A, Stockand JD. (2013). Recording ion channels in isolated, split-opened tubules. “Ion Channels. Methods and Protocols, Second edition.” Methods Mol Biol., 998:341-53.
- Pochynyuk O, Zaika O, O’Neil RG, Mamenko M. (2013). Novel insights into TRPV4 function in the kidney. Pflugers Archiv., 465(2):177-86.
- Zaika OL, Mamenko M, Palygin O, Boukelmoune N, Staruschenko A, Pochynyuk O. (2013). Direct inhibition of basolateral Kir4.1/5.1 and Kir4.1 channels in the cortical collecting duct by dopamine. Am J Physiol Renal Physiol., 305(9): F1277-87.
- Zaika O, Mamenko M, Berrout J, Boukelmoune N, O’Neil RG, Pochynyuk O. (2013). TRPV4 dysfunction promotes renal cystogenesis in autosomal recessive polycystic kidney disease. J Am Soc Nephrol., 24: 604-616.
- Zaika O, Mamenko M, Staruschenko A, and Pochynyuk O. (2013). Direct activation of ENaC by Angiotensin II: recent advances and new insights. Curr Hypertension Reports, 15(1):17-24.
- Berrout J, Jin M, Mamenko M, Zaika O, Pochynyuk O, O’Neil RG. (2012). Function of TRPV4 as a mechanical transducer in flow-sensitive segments of the renal collecting duct system. J Biol Chem, 287:8782-8791.
- Mamenko M, Zaika O, Doris PA, and Pochynyuk O. (2012). Salt-dependent inhibition of ENaC-mediated sodium reabsorption in the aldosterone-sensitive distal nephron by bradykinin. Hypertension, 60:1234-1241.
- Mamenko M, Zaika O, Ilatovskaya D, Staruschenko A, and Pochynyuk O. (2012). Angiotensin II increases activity of the Epithelial Na+ Channel (ENaC) in the distal nephron additively to aldosterone. J Biol Chem., 287(1):660-71.
- Mamenko M, Zaika O, O’Neil RG, and Pochynyuk O. (2012). Ca2+ imaging as a tool to assess TRP channel function in murine distal nephrons. IN: Ion Channels. Methods and Protocols, N. Gamper, ed, (In Press).
- Pochynyuk O, Zaika O, O’Neil RG, Mamenko M. (2012). Novel insights into TRPV4 function in the kidney. Pflugers Arch., (In Press).
- Zaika O, Mamenko M, Berrout J, Boukelmoune N, O’Neil R, and Pochynyuk O. (2012). TRPV4 dysfunction determines renal cystogenesis in a rat model of autosomal recessive polycystic kidney disease. J Am Soc Nephrol., (accepted).
- Zaika O, Mamenko M, Staruschenko A, and Pochynyuk O. (2012). Direct activation of ENaC by Angiotensin II: recent advances and new insights. Current Hypertension Reports, (epub ahead of print).
- Awayda MS, Awayda KL, Pochynyuk O, Bugaj V, Stockand JD, Ortiz RM. (2011). Acute cholesterol induced anti-natriuretic effects- role of epithelial Na+ channel activity, protein levels and processing. J Biol Chem., 21;286(3):1683-95.
- Kucher V, Boiko N, Pochynyuk O, and Stockand JD. (2011). Voltage-dependent gating underlies loss of ENaC function in pseudohypoaldosteronism type 1. Biophys J., Vol 100(8): 1930-9.
- Mamenko, M, Zaika, O, Jin, M, O’Neil, RG, and Pochynyuk, O. (2011) Purinergic activation of Ca2+-permeable TRPV4 channels is essential for mechano-sensitivity in the aldosterone-sensitive distal nephron. PLoS One, 6(8):e22824
- Pochynyuk O, Stockand JD. (2011). Role of Collecting Duct AT1a Receptors in Concentrating Urine (editorial focus). J Am Soc Nephrol., 22(12):2144-5.
- Zaika O, Mamenko M, O’Neil RG, and Pochynyuk O. (2011). Bradykinin acutely inhibits activity of the epithelial Na+ channels (ENaC) in mammalian aldosterone-sensitive distal nephron. Am J Physiol Renal Physiol., Vol 300(5):F1105-15.
- Chen L, Wu H, Pochynyuk O, Reisenauer MR, Zhang Z, Huang L, Zaika OL, Mamenko M, Zhang W, Zhou Q, Liu M, Xia Y, Zhang W. (2011). Af17 Deficiency Increases Sodium Excretion and Decreases Blood Pressure. J Am Soc Nephrol., Vol 22(6):1076-86.
- Stockand JD, Mironova E, Bugaj V, Rieg T, Insel PA, Vallon V, Peti-Peterdi J, and Pochynyuk O. (2010). Purinergic inhibition of ENaC produces aldosterone escape. J Am Soc Nephrol., Vol. 21(11):1903-11.
- Pochynyuk O, Rieg T, Bugaj V, Schroth J, Yokoyama U, Insel PA, Stockand JD, and Vallon V. (2010). Dietary Na+ inhibits ENaC open probability in cortical collecting duct by enhancing apical ATP/P2Y2 receptor tone. FASEB J., Vol. 24(6):2056-65
- Pochynyuk O, Mironova E, Kucher V, Boiko N, Staruschenko A, Karpushev A, Tong Q, Hendron E, and Stockand J. (2009). Disruption of a conserved Trp at the base of transmembrane domain 1 confers voltage sensitivity to the epithelial Na+ channel. J Biol Chem., Vol 284(38):25512-21.