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W Gil Wier
Ph.D.
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| Academic Title:
Professor |
| Primary Appointment:
Physiology |
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gwier001@umaryland.edu |
| Location:
660 West Redwood St.
HH 525 |
| Phone:
410-706-3349 |
| Fax:
410-706-8341 |
| Lab:
410-706-3925 |
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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.
Publications
1. Murphy, T.H., Baraban, J.M., Wier, W.G. and Blatter, L.A. (1994) Visualization of quantal synaptic transmission by dendritic calcium imaging. Science 263:529-532.
2. Murphy, T.H, Baraban, J.M. and Wier, W.G. (1995) Mapping miniature synaptic currents to single synapses using calcium imaging reveals heterogeneity in postsynaptic output. Neuron 15:159-168.
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. Lamont, C., Vainorius, E., and Wier, W.G. (2003) Purinergic and Adrenergic Ca2+ transients during neurogenic contractions of rat mesenteric small arteries. J Physiol (Lond). 549: 801-808. PDF | Movie for Fig. 2 | Movie for Fig. 4
7. Mauban, J.R.H. and Wier, W.G. (2004) Essential Role of EDHF in the Initiation and Maintenance of adrenergic vasomotion in rat mesenteric arteries. Am. J. Physiol. Heart & Circ. 287: H608-H616.
8. Lamont, C., Vial, C., Evans, R.J. and Wier, W.G. (2006 Aug 18) Purinergic neurogenic transmission is absent in small arteries of P2X1 null mice. Am. J. Physiol. Heart & Circ Physiol. 291: H3106-H3113.
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