Personal History:After receiving a Ph.D. in Physiology in 1978 from the University of Utah in Salt Lake City, I did post-doctoral work with Dr. John R. Blinks in the Department of Pharmacology at the Mayo Foundation in Rochester, MN. There, we made some of the first measurements of Calcium ion concentration in heart muscle, using the photoprotein, aequorin. I then joined the faculty of the University of Maryland at Baltimore in 1982 where my research has been funded continuously by NIH. In addition to being a ‘calciumologist’, I teach cardiovascular physiology to first-year medical students. I'm on the faculty of the interdepartmental training programs Membrane Biology, and Muscle Biology, and am a member of the University of Maryland Graduate School. I’m also an Adjunct Professor at Xi’an Jiatong University, China.
Research Interests:We are using high resolution imaging to study the role of Ca2+ in adrenergic control mechanisms in intact, pressurized resistance arteries. Imaging Ca2+ in such a preparation is challenging, compared to single isolated cells. It is expected to be highly rewarding however, because of the ability to see [Ca2+]i during truly physiological stimuli, such as pressure, shear stress, or neuronal stimulation. Furthermore, the cells are connected normally (via gap junctions), allowing the observation of cellular communication or co-ordinated activity that cannot exist in isolated cells. This is most important in view of the emerging concept that arterial function is carried out by 'information networks within the arterial wall' (Beny, 1999). While the potential benefits of such preparations are undeniable, the difficulty in imaging Ca2+ in such preparations is that they are thick, scatter light and can move. Nevertheless, our preliminary data shows that with modern optical sectioning techniques (confocal and two-photon) it is possible to observe events within subcellular volumes within part of a much larger scene, comprised of a group of inter-connected cells. In the case of an artery, such a scene can encompass several vascular smooth muscle cells, nerve endings and endothelial cells. Recently, we have been concerned with the mechanisms governing release of the sympathetic neurotransmitters, NE and ATP from sympathetic nerve endings in these arteries. ATP binds to P2X1 receptors to activate inward Ca2+ current and produce a local, non-propagating post-junctional Ca2+ transient that we called a 'jCaT' (junctional Ca Transient). NE binds to a1-adrenoceptors to produce propagating Ca2+ waves. These studies are providing a new picture of Ca2+ signaling in the smooth muscle of arteries. In summary, by obtaining high resolution images of molecular messengers within the walls of intact pressurized arteries, it is hoped that a new, more integrated view of the cellular and inter-cellular mechanisms that control vascular resistance can be obtained.
- Christine Lamont, Ph.D. - Research Associate
- Albert Y. Rhee, Ph.D. - Post-Doctoral Fellow
- Joseph Zacharia, Ph.D. - Post-Doctoral Fellow
- Manxiang Li, M.D. - Post-Doctoral Fellow
1. Murphy, T.H., Baraban, J.M., Wier, W.G. and Blatter,
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3. López-López, J.R., Shacklock, P.S., Balke, C.W. and Wier, W.G. (1995) Local calcium transients triggered by single L-type Ca2+-channel currents in cardiac cells. Science 268:1042-1045.
4. Mauban, J.R.H., Lamont, C., Balke, C.W. and Wier, W.G. (2001) Adrenergic stimulation of rat resistance arteries affects Ca2+ sparks, Ca2+ waves, and Ca2+ oscillations. American Journal of Physiology 280:H2399-H2405.
5. Lamont, C. and Wier, W.G. (2002) Evoked and Spontaneous Purinergic Junctional Ca2+ transients, (jCaTs) in Rat Small Arteries. Circulation Research, 91: 454-456.
6. Mauban, J.R., Zacharia, J., Zhang, J., Wier, W.G. (2012) Vascular Tone and Ca(2+) Signaling in Murine Cremaster Muscle Arterioles in Vivo. Microcirculation. Microcirculation. Nov 9. doi: 10.1111/micc.12025. [Epub ahead of print]
7. Blaustein, M.P., Leenen, F.H., Chen, L., Golovina, V.A., Hamlyn, J.M., Pallone, T.L., Van Huysse, J.W., Zhang, J., Wier, W.G. (2012) How NaCl raises blood pressure: a new paradigm for the pathogenesis of salt-dependent hypertension. Am J Physiol Heart Circ Physiol. 2012 Mar 1;302(5):H1031-49. doi: 10.1152/ajpheart.00899.2011. Epub 2011 Nov 4. Review. PMCID: PMC3311458
8. Zhang, J., Chen, L., Raina, H., Blaustein, M.P., Wier, W.G. (2010) In vivo assessment of artery smooth muscle [Ca2+]i and MLCK activation in FRET-based biosensor mice. Am J Physiol Heart Circ Physiol. 2010 ep;299(3):H946-56. doi: 10.1152/ajpheart.00359.2010. Epub 2010 Jul 9. PMCID: PMC2944472
9. Mauban, J.H., Zacharia, J., Zhang, J., Wier, W.G. (2013) Vascular Tone and Ca2+ Signaling in Murine Cremaster Muscle Arterioles in Vivo. Microcirculation. Apr;20(3):269-77.
10. Zacharia, J., Mauban, J.H., Raina, H., Fisher, S.A., Wier, W.G. (2013) High Vascular tone of mouse femoral arteries in vivo is determined by sympathetic nerve activity via a1a and a1D adrenoceptor subtypes. PloS One, May. PMCID: PMC3680395
11. Zhao, M., He, X., Bi, X.Y. Yu, X.J., Wier, W.G., Zang, W.J.. (2013) Vagal stimulation triggers peripheral vascular protection through the cholinergic anti-inflammatory pathway in a rat model of myocardial ischemia/reperfusion. Basic Res Cardiol Vol 108 Article No. 345
12. Pappano, A.J., Wier, W.G. Cardiovascular Physiology 10th Edition, 2013, Elsevier Mosby, Phila. PA
Links of Interest:Ouabain Hypertension Program Project Grant
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