Mouse Chromaffin Cells Have Two Populations of Dense Core Vesicles

1 Department of Neurobiology, Pharmacology, and Physiology, The University of Chicago; and 2 Department of Anatomy and Cell Biology, University of Illinois, Chicago, Illinois Submitted 25 March 2005; accepted in final form 18 May 2005 The quantal hypothesis states that neurotransmitter is released in discrete packages, quanta, thought to represent the neurotransmitter content of individual vesicles. If true, then vesicle size should influence quantal size. Although chromaffin cells are generally thought to have a single population of secretory vesicles, our electron microscopy analysis suggested two populations as the size distribution was best described as the sum of two Gaussians. The average volume difference was fivefold. To test whether this difference in volume affected quantal size, neurotransmitter release from permeabilized cells exposed to 100 µM Ca 2+ was measured with amperometry. Quantal content was bimodally distributed with both large and small events; the distribution of vesicle sizes predicted by amperometry was extremely similar to those measured with electron microscopy. In addition, each population of events exhibited distinct release kinetics. These results suggest that chromaffin cells have two populations of dense core vesicles (DCV) with unique secretory properties and which may represent two distinct synthetic pathways for DCV biogenesis or alternatively they may represent different stages of biosynthesis. Address for reprint requests and other correspondence: C. P. Grabner, Dept. of Neurobiology, Pharmacology, and Physiology, The University of Chicago, 947 E. 58 th St., Chicago, IL 60637 (E-mail: cpg22{at}email.med.yale.edu )