Intracellular calcium is a critical messenger that triggers neurotransmitter secretion, muscle contraction, and numerous other cellular activities. Some "trigger" calcium comes directly from the extracellular fluid and enters the cells through calcium-selective channels that are opened during cell activity. Much of the "trigger" calcium, however, comes from intracellular stores and is released by other "second messengers." The amount of calcium that is released depends, in part, upon the fractional saturation of the stores; in turn, the amount of calcium released determines the relative magnitude of the cell response. Much of our research program focuses on questions of how cytosolic free calcium is controlled, and how the calcium content within intracellular stores is regulated in neurons, astroglia, and vascular smooth muscle cells.
We study a variety of aspects of calcium metabolism in freshly isolated nerve terminals and vascular smooth muscle cells, in arterial rings, and in cultured neurons, astroglia, and arterial muscle cells. In some studies, we employ novel high resolution digital imaging methods with calcium-sensitive dyes to measure, directly, selective release of calcium from individual storage sites, and the movement of calcium from one compartment to another. In other studies, we use dyes that label the organelles that store calcium, and antibodies (for immunocytochemistry) that specifically label the various proteins involved in transporting or regulating the movements of calcium across the plasma membrane and the Mordecai Blaustein, continued membranes of intracellular organelles. Pharmacological agents and molecular biological methods (e.g., antisense oligonucleotides) are employed to activate, inhibit, or knock out individual transport systems.
A second major focus of our research program is on the unique role of the plasmalemmal sodium gradient in the control of calcium extrusion and intra-organellar calcium regulation. One of our goals is to determine whether arterial smooth muscle cell calcium metabolism is secondarily altered in hypertension as a result of a primary defect in sodium metabolism. We are also interested in elucidating the mechanisms that, as a result of calcium overload, lead to cell injury and cell death. These mechanisms may play a role in the neuropathology of aging, in Alzheimer's disease, in chronic epilepsy, and in many other neuronal diseases.
A third area of research is focused on potassium channels, in neurons and smooth muscle. We are using recombinant methods to study the structure-function relationships between polypeptide toxins from scorpion and snake venoms and their selective interactions with specific classes of potassium channels. Certain types of potassium channels play critical roles in regulating free calcium levels and cellular activity in a variety of cell types. The toxins are used as tools to help determine the functions of specific potassium channels.
Slodzinski, M.K., Juhaszova, M., and Blaustein, M.P., "Antisense inhibition of Na+Ca2+ exchange in primary cultured arterial myocytes," American Journal of Physiology, 1995.