Exploring Local Calcium Feedback: Trying to Fool Mother Nature

The job of nature is to design robust organisms. To this end, it often employs a classical engineering strategy: provide excess functional capacity and enclose it in regulatory, preferably redundant, feedback loops that function not only at the sub-cellular level, but also at the molecular, or nanoscale, levels. The job of the physiologist is to discover the mechanisms that lie within the feedback loops. Because the properties of a well designed feedback loop are determined by its function rather than its mechanism, physiologists can expect to meet with nature's active resistance to their efforts. Both stealth and cunning are called for: stealth to get within the feedback loops and disable, or at least weaken, them, and cunning because it seldom will be possible to entirely disable a feedback loop, so the results of any weakening of the loop must be compared with quantitative models. To make matters worse, molecular-scale...