The research interests in my laboratory concern the mechanisms controlling calcium ion fluxes in excitable cells, especially skeletal muscle and neurons. Stimulation of these cells causes calcium ions to be released from the intracellular calcium-sequestering organelle, the endoplasmic or sarcoplasmic reticulum. The resulting elevation of cytosolic calcium serves as a "second messenger" in these cells, causing contraction in muscle or activation of metabolic processes in neurons. The techniques for measuring these changes in intracellular calcium involve the use of electrophysiological methods to stimulate the cell, and confocal optical imaging techniques to measure changes in the fluorescence of a calcium indicator within the cytosol. We have recently discovered in skeletal muscle that calcium ions are released in small, discrete amounts. During small depolarization of the membrane potential, these calcium release events, or calcium "sparks", appear as brief elevations of calcium of about 100 nanomolar, lasting 20 milliseconds. These release events are caused by the opening of individual (or a few) calcium release channels in the membrane of the sarcoplasmic reticulum. In addition to events caused by changes of membrane potential, we have also observed sparks caused by cytosolic calcium itself, activated by a mechanism known as calcium-induced calcium release. These studies will allow us to examine the activation of calcium release at the level of single release channels, so as to characterize the voltage and calcium dependence of channel activation in situ.
Klein, M.G., Cheng, H., Santana, L.F., Jiang, Y.-H., Lederer, W.J., and Schneider, M.F., "Two mechanisms of quantized calcium release in skeletal muscle", Nature 379:455-458, 1996.
Klein, M.G., Lacampagne, A., and Schneider, M.F. 1997. Voltage dependence of the pattern and frequency of discrete Ca2+ release events after brief repriming in frog skeletal muscle. Proc. Nat'l. Acad. Sci. 94:11061-11066.