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Department of Pharmacology

University of Nevada School of Medicine

Reno, Nevada

Faculty Member
Image of Hume Joseph R. Hume, Professor
Telephone:
Email:
(775) 784-1731 email
Fax: Location:
(775) 784-1620
Manville 1
About Dr. Hume
Background Information on Joseph Hume:

Professor and Chairman, University of California, San Francisco, Ph.D., 1979; Director, Center of Biomedical Research Excellence (COBRE). Cardiac and smooth muscle electrophysiology, pharmacology and molecular biology of ion channels.
Research Interests
My areas of research interests include cardiac and smooth muscle electrophysiology and pharmacology, and excitation-contraction coupling mechanisms. One of the major contributing causes of death following acute myocardial infarction is the development of electrical disorders of the heart (arrhythmias). Antiarrhythmic drug therapy is used clinically to correct and prevent occurrences of these arrhythmias. A primary research goal of my laboratory is to gain a better understanding of the electrical properties of cardiac muscle at the level of individual cells and how these properties are modified by various pharmacological agents. We are also interested in gaining a better understanding of the electrical activity of individual smooth muscle cells isolated from a variety of blood vessels (including renal and pulmonary arteries). A more complete understanding of the relationship between electrical activity and mechanical tone in these cells could lead to the development of new antihypertensive agents.

Individual myocytes can be isolated from the heart or blood vessels by utilizing an enzymatic dispersion method. The application of the patch clamp technique allows ion channels responsible for the action potential and resting membrane potential to be studied quantitatively. It is also possible to combine the patch clamp technique with calcium-sensitive dyes internally perfused to study the relationship between ion channel activity and changes in intracellular calcium concentration in single cells. Using these methods we have recently characterized the properties of a number of different chloride channels in heart and vascular smooth muscle cells, as well as the properties of ion channels in pulmonary arterial smooth muscle cells whose activity is dependent upon oxygen tension. In collaboration with other investigators associated with the Center of Biomedical Research Excellence (COBRE), we have recently cloned several chloride channels from heart and are performing structure-function studies of these proteins and using functional genomic approaches to determine their physiological and possible pathophysiological role in human cardiovascular function and disease, and are actively investigating their the regulation of calcium channels in smooth muscle cells by intracellular cyclic nucleotides and G proteins.
Published Work
Selected Publications
  1. Janiak, R., Wilson, S.M., Montague, S. &; Hume, J.R. Heterogeneity of calcium stores and elementary release events in canine pulmonary arterial smooth muscle cells. Am. J. Physiol. 280: C22-C33, 2001.
  2. Duan, D., Zhong, J., Hermoso, M., Satterwhite, C.M., Rossow, C.F., Hatton, W.J., Horowitz, B. &; Hume, J.R. Functional inhibition of native volume-sensitive outwardly rectifying anion channels in muscle cells and Xenopus oocytes by anti-ClC-3 antibody. J. Physiol. Lond. 531.2, 437-444, 2001.
  3. Zhong, J., Hume, J.R. &; Keef, K.D. ?-adrenergic stimulation of vascular L-type Ca2+ channels involves both G protein ?s and ?? subunits. J. Physiol. Lond. 531.1: 105-115, 2001.
  4. Walker, R.L., Hume, J.R. &; Horowitz, B. Differential expression and alternative splicing of TRP channel genes in smooth muscles. Am. J. Physiol. 280: C1184-C1192, 2001.
  5. Keef, K.D., Hume, J.R. and J. Zhong. Invited Review: Regulation of cardiac and smooth muscle Ca2+ channels (Cav1.2a, b) by protein kinases. Am. J. Physiol. 281: C1743-C1756, 2001.
  6. Zhong, J., Wang, G.-X., Hatton, W.J., Yamboliev, I.A., Walsh, M.P. &; Hume, J.R. Regulation of volume-sensitive outwardly rectifying anion channels in vascular smooth muscle cells by protein kinase C. Am. J. Physiol. 283: C1627-C1636, 2002.
  7. Wilson, S.M., Nicholson, N., Johnston, L., Janiak, R., Smith, G.D. &; Hume, J.R. Comparative capacitative calcium entry mechanisms in canine pulmonary and renal arterial smooth muscle cells. J. Physiol. Lond. 543.3, 917-931, 2002.
  8. Hermoso, M., Satterwhite, C.M., Andrade, Y., Hidalgo, J., Wilson, S., Horowitz, B. &; Hume J.R. ClC-3 is a fundamental molecular component of volume-sensitive outwardly rectifying Cl- channels and volume regulation in Hela cells and Xenopus laevis oocytes. J. Biol. Chem. 277: 40066-40074, 2002.
  9. Wang, G.-X., Hatton, W.J., Wang, G.L., Zhong, J., Yamboliev, I., Duan, D. &; Hume, J.R. Functional effects of novel anti-ClC-3 antibodies on native volume-sensitive osmolyte and anion channels (VSOACs) in cardiac and smooth muscle cells. Am. J. Physiol.H1453-H1463, 2003.
  10. Hume, J.R. &; Grant, A.O. Agents used in cardiac arrhythmias. In: Basic and Clinical Pharmacology, B. G. Katzung (ed.), ninth edition, McGraw-Hill, New York, NY, p.216-240, 2003.
  11. Wang, G.-X., McCrudden, C., Dai, Y.-P., Horowitz, B., Hume, J.R. & Yamboliev, I.A. Hypotonic activation of volume-sensitive outwardly-rectifying chloride channels in cultured PASMCs is modulated by SGK. Am. J. Physiol. 287: H533-H544, 2004
  12. Yamamoto-Mizuma, S., Wang, G.-X., Hatton, W.J., Duan, D., Horowitz, B., Lamb, F.S. & Hume, J.R. Altered properties of volume-sensitive osmolyte and anion channels (VSOACs) and membrane protein expression in cardiac and smooth muscle myocytes from Clcn3-/- mice. J. Physiol. 557.2: 439-456, 2004
  13. Yamamoto-Mizuma, S., Wang, G.-X. & Hume, J.R. P2Y purinergic receptor regulation of CFTR chloride channels in mouse cardiac myocytes. J. Physiol. 556.3:727-737, 2004
  14. Hume, J.R. and M.T. Nelson. In Memoriam. Burton Horowitz. Circ. Res. 94: 1151, 2004
  15. Wilson, S.M., Mason, H.S., Montague, S., Johnston, L., Nicholson, N., Mansfield, S. & Hume J.R. Role of basal extracellular Ca2+ entry during 5-HT induced vasoconstriction of canine pulmonary arteries. British J. Pharmacol. 144:252-264, 2005.
  16. Ng, L.C., Wilson, S.M. & Hume, J.R. Mobilization of sarcoplasmic reticulum stores by hypoxia leads to consequent activation of capacitative Ca2+ entry in isolated canine pulmonary arterial smooth muscle cells. J. Physiol. 563:409-419, 2005.
  17. Dai, Y.-P., Bongalon, S., Hatton, W.J., Hume, J.R. & Yamboliev, I.A. ClC-3 chloride channel is upregulated by hypertrophy and inflammation in rat and canine pulmonary artery. British J. Pharmacol. 145:5-14, 2005.
  18. Wang, G.L., Wang, G.-X., Yamamoto, S. Ye, L., Baxter, H., Hume, J.R., and Duan, D. Molecular mechanisms of regulation of fast-inactivating voltage-dependent transient outward K+ current in mouse heart by cell volume changes. J. Physiol. 568 423-443, 2005.
  19. Britton, F.C., Wang, G.L., Ye, L., Horowitz, B., Hume, J.R. & Duan, D. Functional characterization of alternatively spliced cardiac ClC-2 chloride channel variants in mammalian cell lines. J. Biol. Chem. 280:25871-25880, 2005.
  20. Wang, G.-X., Dai, Y.-P., Bonggalon, S., Hatton, W.J., Murray, K., Hume, J.R. & Yamboliev, I.A. Hypotonic activation of volume-sensitive outwardly rectifying anion channels (VSOACs) requires coordinated remodeling of subcortical and perinuclear actin filaments. J. Memb. Biol. 208:15-26, 2005.
  21. Duan, D., Lui, L., Bozeat, N., Huang, M., Xiang, S.Y., Ye, L. & Hume, J.R. Functional role of anion channels in cardiac diseases. Acta Pharmacol. Sinica 26(3): 265-278, 2005.
  22. Rossow, C.F., Duan, D., Hatton, W.J., Britton, F., Hume, J.R. & Horowitz, B. Functional role of amino terminus in ClC-3 chloride channel regulation by phosphorylation and cell volume. Acta Physio. Scand. 187:5-19, 2006.
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