Calcium in the function of the nervous system: new implications.

0 d inue to beat [1]. This was a key discovery that led to introuction of a famous physiological solution, acknowledged y subsequent generations of physiologists as “Ringer’s soution”. Since then, a large variety of functions have been stablished for this almost universal intracellular messenger. alcium controls a diverse range of cellular processes, such s gene transcription [2], ion channel function [3], muscle ontraction and cell proliferation [4]. To control multiple unctions specifically, the distribution of Ca2+ is highly reglated in the dimensions of space, time and concentration 5,6]. The existence of Ca2+ microdomains was recognized a ecade ago. In 1992, Augustine and Neher wrote “Intracelular Ca2+ (Cai) signals should be restricted to spatial comartments of very small volume (typically less than 1 m in iameter). Within such tight quarters, the rises in Ca are pretal observations, obtained by Katz and co-workers [17,18], provided convincing evidence of the pivotal role of Ca2+ for neurotransmitter release. The first clear evidence was presented by Katz and Miledi [17] in elegant experiments on the frog motor nerve terminal. The preparation was immersed in a Ca2+-free Ringer’s solution and a focal electrode filled with 0.5 M CaCl2 was placed on a synaptic spot. This electrode was the only source of controlled application of Ca2+. The same electrode was also used for extracellular recording of preand post-synaptic responses to nerve stimulation (see scheme in Fig. 1A). When a strong negative potential was applied to the pipette to stop Ca2+ efflux, only pre-synaptic deflection was observed (Fig. 1B, b). Decreasing the negative voltage allowed release Ca2+ from the pipette and resulted in appearance of post-