Areas of Interest
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. |
