Near simultaneous release of classical and peptide cotransmitters from chromaffin cells.

Adrenal chromaffin cells are an important part of the neuroendocrine system and under stressful conditions release catecholamines into the blood, thus regulating many physiological processes. In addition to the catecholamines, chromaffin cells also synthesize a range of peptides, including neuropeptide Y. Although the catecholamines and peptides are both contained within dense core granules, whether they are copackaged is less clear. Here, I investigate whether a single dense core granule can be loaded with both types of transmitter molecules. Using amperometry and FMRFamide tagging, I simultaneously measure the secretion of the catecholamines and a neuropeptide from mouse chromaffin cells in vitro. I find that fusion of a single dense core granule releases both types of transmitters into the extracellular space. Significant amounts of peptide escape from a fusing granule in 1-2 ms: almost as rapidly as the catecholamines. This suggests that the kinetics of peptide secretion might not be as sluggish as sometimes thought.