Facilitation as a tool to study the entry of calcium and the mechanism of neurotransmitter release

We have shown the usefulness of using facilitation as an indirect tool for measuring release-related processes that cannot be measured directly. Most of the findings obtained by measuring facilitation have been verified (by various groups) by direct measurements in systems where such measurements could be carried out. This provides reassurance that the methodology is sound. Using facilitation one can gain insight into numerous processes that together govern the dependence of release on the intracellular calcium concentration C. The physiological conclusions have been listed in the text. We reiterate some of these conclusions here, in order to emphasize certain additional matters. For 20 years it has been known that release is a saturating cooperative function of the extracellular Ca2+ concentration Ce (Dodge and Rahamimoff, 1967). Yet several questions remained open, such as whether this behavior in fact reflected the dependence of the release on the intracellular Ca2+ concentration C, of entry on Ce, or of a combination of these individual possibilities. We have found, using short-term facilitation as the investigatory tool, that release is a saturating cooperative function of C. It is obvious that saturation will eventually take place as C increases. What is important to emphasize is that the saturation occurs at physiological values of C. Such values typically correspond to the amount of Ca2+ that enters following only one or very few pulses. Various aspects of facilitation F can be used to characterize the processes responsible for the removal of the calcium that enters the nerve terminal. Here we emphasized the role of the duration of F, but information can also be obtained by examining other aspects of facilitation (Parnas and Segel, 1980; H. Parnas et al., 1982; I. Parnas et al., 1982a). The principal conclusion is that removal shows saturation kinetics.(ABSTRACT TRUNCATED AT 250 WORDS)