Sub-quantal release is not dominant during prolonged depolarization in adrenal chromaffin cells

Exocytosis, which mediates important functions like synaptic transmission and stress responses, has been postulated to release all transmitter molecules in the vesicle in the "all-or-none" quantal hypothesis. Challenging this hypothesis, amperometric current recordings of catecholamine release propose that sub-quantal or partial transmitter release is dominant in various cell types, particularly chromaffin cells. The sub-quantal hypothesis predicts that fusion pore closure (kiss-and-run fusion), the cause of sub-quantal release, is dominant, and blocking pore closure increases quantal size. We tested these predictions by imaging fusion pore closure and amperometric recording of catecholamine release in chromaffin cells during high potassium application, the most-used stimulation protocol for sub-quantal release study. We found that fusion pore closure is not predominant, and inhibition of the fusion pore closure does not increase the quantal size calculated from the amperometric current charge when a sufficiently long integration time is used. These results suggest that sub-quantal release is not prevalent during high potassium application in adrenal chromaffin cells.