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Withrow Gil Wier, PhD

Academic Title:

Adjunct Professor

Primary Appointment:

Physiology

Location:

660 West Redwood St. HH 525

Phone (Primary):

410-706-3349

Fax:

410-706-8341

Highlighted Publications

Mauban, J.H., Zacharia, J., Zhang, J., Wier, W.G. (2013)  Vascular Tone and Ca2+ Signaling in Murine Cremaster Muscle Arterioles in VivoMicrocirculation. Apr;20(3):269-77.

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 subtypesPloS One, May.  PMCID: PMC3680395

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/reperfusionBasic Res CardiolVol 108 Article No. 345

Pappano, A.J., Wier, W.G. Cardiovascular Physiology 10th Edition, 2013, Elsevier Mosby, Phila. PA

Wier, W.G.  (2014).  More in vivo experimentation is needed in cardiovascular physiology.  American Journal of Physiology.  15 July 2014Vol. 307no. H121-H123DOI: 10.1152/ajpheart.00326.2014.  PMCID: PMC4101641

He, X., Bi, X.Y., Lu, X.Z., Zhao, M., Yu, X.J., Sun, L., Xu, M., Wier, W.G., Zang W.J.  Reduction of Mitochondria-Endoplasmic Reticulum Interactions by Acetylcholine Protects Human Umbilical Vein Endothelial Cells From Hypoxia/Reoxygenation Injury. Arterioscler Thromb Vasc Biol. 2015 Jul;35(7):1623-34. doi: 10.1161/ATVBAHA.115.305469. Epub 2015 May 14.  

Blaustein, M.P., Chen, L., Hamlyn, J.M., Leenen, F.H., Lingrel, J.B., Wier, W.G., Zhang, J.  Pivotal role of α2 Na+ pumps and their high affinity ouabain binding site in cardiovascular health and disease.  J Physiol. 2016 Jun 28. doi: 10.1113/JP272419. [Epub ahead of print]

Additional Publication Citations

Murphy, T.H., Baraban, J.M., Wier, W.G. and Blatter, L.A. (1994) Visualization of quantal synaptic transmission by dendritic calcium imagingScience 263:529-532.

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.

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.

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+ oscillationsAmerican Journal of Physiology 280:H2399-H2405.

Lamont, C. and Wier, W.G.  (2002) Evoked and Spontaneous Purinergic Junctional Ca2+ transients, (jCaTs) in Rat Small ArteriesCirculation Research, 91: 454-456.

Mauban, J.R., Zacharia, J., Zhang, J., Wier, W.G. (2012) Vascular Tone and Ca(2+) Signaling in Murine Cremaster Muscle Arterioles in Vivo. MicrocirculationMicrocirculation.  Nov 9. doi: 10.1111/micc.12025. [Epub ahead of print]

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 hypertensionAm 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

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 miceAm J Physiol Heart Circ Physiol. 2010 ep;299(3):H946-56. doi: 10.1152/ajpheart.00359.2010. Epub 2010 Jul 9.  PMCID: PMC2944472

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.

Grants and Contracts

1R01HL122827 0401/2016 - 03/31/2020. "Creation of Optical Biosensor Mice for Longitudinal Studies of Vascular Function".  MPI grant with Mark Rizzo. 

Links of Interest