MICROMOLAR 4-AMINOPYRIDINE ENHANCES INVASION OF A VERTEBRATE NEUROSECRETORY TERMINAL ARBORIZATION - OPTICAL-RECORDING OF ACTION-POTENTIAL PROPAGATION USING AN ULTRAFAST PHOTODIODE-MOSFET CAMERA AND A PHOTODIODE-ARRAY

Modulation of the amount of neuropeptide released from a neurosecretor y tissue may be achieved by different means. These include alterations in the quantity secreted from each active nerve terminal or in the ac tual number of terminals activated. From the vertebrate hypothalamus, magnocellular neurons project their axons as bundles of fibers through the median eminence and infundibular stalk to arborize extensively an d terminate in the neurohypophysis, where the neurohypophysial peptide s and proteins are released into the circulation by a Ca-dependent mec hanism. Elevating [Ca2+](o) increases the magnitude of an intrinsic op tical change in the neurohypophysial terminals that is intimately rela ted to the quantity of neuropeptide released. Similarly, the addition of micromolar concentrations of 4-aminopyridine to the bathing solutio n enhances this change in large angle light scattering. However, we sh ow here that, while these effects are superficially similar, they refl ect different mechanisms of action. Evidence from intrinsic optical si gnals (light scattering) and extrinsic (potentiometric dye) absorption changes suggests that calcium increases the amount of neuropeptide re leased from each active terminal in the classical manner, while 4-amin opyridine exerts its secretagogue action by enhancing the invasion of action potentials into the magnocellular neuron's terminal arborizatio n, increasing the actual number of terminals activated. Physiologicall y, electrical invasion of the complex terminal arborization in the neu rohypophysis may represent an extremely sensitive control point for mo dulation of peptide secretion. This would be especially effective in a neurohaemal organ like the posterior pituitary, where, in contrast wi th a collection of presynaptic terminals, the precise location of rele ase is less important than the quantity released.