How large is a fusion pore?

The fusion pore is an important focus of research in exocytosis. It tracks the onset and progress of secretion from a vesicle, and its structure has important implications for the mechanism of membrane fusion. Fusion pores can be visualized with structural methods, and the diameter can be estimated by various physiological techniques that measure flux. Estimates of fusion pore size vary widely, and the divergent results have been a source of confusion. This Perspective assesses the different approaches to determining the diameter of a fusion pore. Focusing on the initial state immediately after opening helps to identify a distinct and fundamental structure. Pore diameters estimated from flux measurements generally depend on modeling the pore as a cylinder. A critical assessment of this model based on experimental data from ion channels suggests that this approach systematically underestimates the diameter. Taking these factors into account narrows the range of sizes for initial fusion pores, reconciles some of the disparities, and highlights variations likely to have a biological basis.