Porocytosis: Fusion Pore Array Secretion of Neurotransmitter

Abstract

We believe that there is sufficient experimental evidence to support the premise that transmitter is secreted by the simultaneous activation of arrays of fusion pores at docked vesicles. This process is initiated by the action potential that activates calcium channels to increase the number of cytoplasmic calcium ions. Calcium ions trigger fusion pores to flicker open causing transmitter to diffuse from vesicular stores. We define the term porocytosis to identify this process and use the term synaptomere to indicate the anatomical and physiological functional unit of the synapse or junction. Our model shows that the simultaneous flicker of fusion pores in an array can generate unitary-end plate potentials (u-EPPs) and miniature end plate potentials (MEPPs) and that activation of all fusion pores produces EPPs. U-EPPs and EPPs generated with the model show mean values and coefficients of variation similar to experimental observations. The model is robust in that the number of docked vesicles can vary and these can be full to empty depending on nerve frequencies and vesicular traffic. The model shows that the overall process of excitation-secretion coupling is highly deterministic. At the neuromuscular junction, secretion from arrays of fusion pores ensures that a muscle fiber action potential is always produced over a range of frequencies because all transmitter release sites are activated. Our model shows that transmission at the synaptomere guarantees fidelity of information transfer at different frequencies. This characteristic shows a dynamic relationship of the secretory process to memory and learning.