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).

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