An electron microscopy study of changes in dense core vesicles of PC12 cells following pulse depolarization

Depolarization of PC12 cells by brief pulses of high K+ or ATP produces electrophysiological responses consistent with the quantal release of ATP. Quantitative electron microscopy was used to validate whether the same protocol changed dense core vesicles containing endogenous ATP. The total vesicle number fell by 54% after high K+ and by 21% after ATP. Perimembrane vesicles were significantly depleted by high K+, yet unchanged by ATP, suggesting differential contribution by vesicle pools to distinct stimuli during the release process. Vesicle changes were consistent with vesicular release mechanisms for the liberation of discrete packets of endogenous ATP. These data thus support the use of clustered PC12 cells as a model to study the process of ATP release.