Dr. Alicia Ortega Aguilar 
aortega@servidor.unam.mx
Characterization of the calcium transportation mechanisms through different
submembrane fractions of muscle cells
OBJECTIVES
- To characterize and do a comparative study of the different mechanisms
of calcium movement in the cells of fast, slow and diaphragm skeletal muscles.
The differences found will help us to understand, in general, the principle
of many muscular dysfunctions and will provide us with elements to support
the membrane hypothesis of the physiological phenomenon of fatigue.
- To study the correlation that exists between thermal inactivation and the
conformational stability of muscle cell integral membrane proteins, as a tool
to study the relationship between bilayer lipid composition and the activity
of calcium transporting proteins, principally the effect of cholesterol and
drugs that interact with calcium fixing proteins.
- To model the mechanism through which damage to the sarcolemma of skeletal
muscular fiber can be restored after the extracellular addition of phospholipids.
SUMMARY
The main events leading to muscle activation are: The electric depolarization
of the sarcolemma followed by a massive output of calcium from the sarcoplasmic
reticulum and the binding of calcium to the myofibrils in order for a contraction
to take place. Calcium regulating proteins, like Ca+2 ATPase and the Na2/Ca+2
exchanger, are considered to be the most important membrane components regulating
the expulsion of calcium through the membranes of normal, apoptosic and neoplastic
cells. Integral membrane proteins are regulated by the lipid composition of the
membrane, principally by cholesterol which has an inhibitory effect on the activity
of calcium transporting proteins. An understanding of how the calcium transport
mechanisms are regulated is essential to explaining the physiology and pathology
of the muscle cell. The characterization of the calcium transport mechanisms through
the transversal tubules of the fast, slow and diaphragm skeletal muscles gives
elements with which to study the possible influence of the integrity of these
mechanisms on muscle fatigue.
- The study of the thermodynamic properties of Ca+2 ATPase and the Na+/Ca+2
exchanger in native and cholesterol depleted membranes of the T-tubules gives
us information as to how these proteins are regulated by cholesterol
- The study of the effect of drugs like calcium blockers and dehydroprostaglandin
derivatives on the activity and thermal stability of calcium regulating proteins
of the sarcolemma and the sarcoplasmic reticulum of the cardiac myocyte and
skeletal muscular fiber helps us to understand the mechanism through which these
drugs and extracellularly added phospholipids revert sarcolemmal damage produced
mechanically and the deleterious effects of ischemia.
PARTICIPANTS
-
Dr. Hugo González-Serratos
- Rocío Alvarez, B.Sc.
- Sandra Indiana Bajaña, M.Sc.
- Viola Ma. Becker, M.Sc.
BIBLIOGRAPHY
- 1. González-Serratos H., Rozyka M. and Ortega A. Membrane resealing
and restoration of contractility after mechanical injury in frog skeletal
muscle. Proceedings of the National Academy of Sciences, USA. (in press).
- 2. Ortega, A. Santiago J. Mas-Oliva J. and Lepock J. 1996. Cholesterol
increases the thermal stability of the Ca/Mg-ATPase from cardiac microsomes.
Biochem. Biophys. Acta. (in press).
-
3. Ortega, A. González-Serratos H., and Lepock J. 1996 Effect of
the organic Ca+2 channel blocker D-600 on Sarcoplasmic Reticulum Ca2+
Back to Biochemistry Department