Skeletal muscle: three areas of research are carried out in my laboratory: (1) Excitation contraction coupling in normal muscle and during fatigue development. In this area we are studying the following questions: What are the calcium release regulatory mechanisms? What are the muscle calcium homeostatic regulatory mechanisms? What is the biological role of inward Ca currents and the ontogenic evolution of e-c coupling? Images obtained tenti revealed that Ca2+ release is not homogeneous but, that it is composed of spikes of very significant and slow fluctuations which form gradients within the cell cross section area. We are investigating at present what is the mechanism of this stochastic-like type of SR calcium release. We have found that as fatigue develops, groups of myofibrils are not activated and that the areas of maximal Ca2+ release decrease and become sporadic; we are investigating what causes the release inhibition under these circumstances. Since there is a continuous influx of Ca2+ into muscle cells, an homeostatic mechanism must exist to maintain during a long term intracellular Ca2+ at low levels, e.g. Na/Ca exchanger. Finally, we are currently investigating the evolution of inward calcium currents and e-c coupling in embryonic myocytes from Xenopus Laevix. Hugo Gonzalez-Serratos, continued (2) Skeletal muscle calcium handling and mechanical alterations during chronic heart failure. We have found that EDL muscle from rats with chronic heart failure develop half of the specific force and SR calcium release is decreased and the cells have no signs of atrophy. We are currently investigating what caused these alterations which are similar to the ones in the failing heart. (3) Membrane healing and restoration of contractility after mechanical injury. We are investigating a method to heal large (>30 æm) sarcolemmal damages. If a cell is provided with some of the membrane chemicals components it does not deteriorates after the damage. The membrane integrity and contractility recovers. We are currently investigating which would be the most efficient chemical compound combination to produce healing and functional recovery of large carcolemmal damages. We will investigate if this method can be apply to other excitable cells including cardiac myocytes.
Gonzalez-Serratos, H., Rozycha, M., Cordoba-Rodriguez, R., and Ortega, A., "Membrane healing and restoration of contractility after mechanical injury in isolated skeletal muscle fibers from the frog", Proc. Natl. Acad. Sci, 93, 1996.