Blaustein, Mordecai P., M.D., Professor and Chairman
Department of Physiology
E-mail: mblaust@umaryland.edu
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, In Press, 1995.