Exo-endocytosis at mossy fiber terminals: Toward capacitance measurements in cells with arbitrary geometry

Exocytosis and endocytosis are ubiquitous cellular phenomena necessary for diverse functions such as secretion, internal signaling, protein traffic, and motility. Many different techniques have been developed to assay exocytosis and endocytosis, but to date only electrical measurements of plasma membrane capacitance have had the time resolution necessary to capture both the fusion and reuptake of small clear-core vesicle membrane during fast neurotransmission. In this issue of PNAS, Hallermann et al. (1) present capacitance measurements from hippocampal mossy fiber nerve terminals during stimulated exocytosis. These are the first time-resolved membrane capacitance measurements from bona fide (albeit relatively large) bouton-type synaptic terminals, with diameters of ≈3 μm and a resting capacitance of ≈1 pF. The results obtained not only provide important data on basic synaptic properties of this nerve terminal, in particular on the vesicle pool size and the question of multivesicular release, but also provide an example of how to extend capacitance measurements from cells with simple and compact geometry to more general classes of neurons and nerve terminals. The accessibility of exocytosis and endocytosis to voltage-clamp measurements stems from the fact that these processes, by their nature, change the surface area of the plasma membrane. Because the plasma membrane acts as an electrical capacitor, changes in surface area can be detected as changes in its total capacitance. Thus by electrical measurements, net changes in plasma membrane (i.e., exocytosis minus endocytosis) can be measured. Coupled with voltage protocols that open voltagegated calcium channels, this technique can be used to follow membrane changes during Ca2+-dependent secretion of neurotransmitters. If exocytosis and endocytosis are temporally distinct phenomena, the rate of exocytosis can be determined by measuring capacitance jumps triggered by step depolarizations of different durations (see refs. 2–5). In addition, synaptic vesicle membrane retrieval (or reinternalization via endocytosis) …