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Faculty James M. Watras
Associate Professor of Medicine
watras@nso2.uchc.edu
Regulation of inositol 1,4,5-trisphosphate (InsP3)-gated calcium
channels Hormonal activation of InsP3gated Ca channels in vascular
smooth muscle and endothelial cells play a key role in the regulation of
blood pressure. Similarly, activation of InsP3-gated Ca channels in
neurons by various neurotransmitters have been implicated in learning.
Research in our lab is focused on mechanism(s) which modulate the
dynamic range of these channels, thereby limiting the rise in
intracellular Ca following hormonal stimulation of the phosphoinositide
cascade. In the case of vacular smooth muscle, this affects the degree
of vasoconstriction. Particular attention is directed at the mechanism(s)
by which cytosolic Ca modulates the channel, and the characterization of
a recently identified endogenous inhibitor of the InsP3-gated Ca
channel. Mechanisms underlying contractile abnormalities in failing
hearts
A second area of research concerns mechanisms contributing to the
altered intracellular Ca (and hence slowed contraction/relaxation) of
the myocardium in patients with congestive heart failure. Particular
attention is being directed at the possibility that increased expression
of Ca/phospholipid binding proteins (annexins) contribute to the
abnormal myocardial contraction of failing hearts (by slowing Ca
sequestration by intracellular Ca pumps).
Selected Publications:
Xu C, Watras J, Loew LM. 2003. Kinetic analysis of receptor-activated
phosphoinositide turnover. J Cell Biol. May 26;161(4):779-91.
Fink CC, Slepchenko B, Moraru II, Watras J, Schaff JC, Loew LM. 2000.
An image-based model of calcium waves in differentiated neuroblastoma
cells. Biophys J. Jul;79(1):163-83.
Watras J, Orlando R, Moraru II. 2000. An endogenous sulfated
inhibitor of neuronal inositol trisphosphate receptors. Biochemistry.
Mar 28;39(12):3452-60. |
