Direct modulation of the secretory machinery underlies PKA-dependent synaptic facilitation in hippocampal neurons. 1996

L E Trudeau, and D G Emery, and P G Haydon
Department of Zoology and Genetics, Iowa State University, Ames 50011, USA.

Activation of protein kinase A (PKA) is known to facilitate synaptic transmission. Using synapses established by hippocampal neurons in culture, we show that dialysis of PKA inhibitors in the presynaptic neuron blocks synaptic facilitation produced by the adenylyl cyclase activator forskolin, demonstrating a presynaptic locus of action. Using ruthenium red, a tool that is known to stimulate exocytosis independently of Ca2+ influx, but in a manner sensitive to tetanus toxin, we find that the secretory process is directly up-regulated under conditions where the number of functional terminals remains unchanged, as revealed by imaging of FM1-43, a vital indicator of synaptic vesicle endocytosis. Taken together with our ultrastructural analysis that suggests no enhancement of docking, our data indicate that PKA causes synaptic facilitation by directly elevating the probability of exocytosis of individual vesicles in response to an invariant Ca2+ signal.

UI MeSH Term Description Entries
D007395 Interneurons Most generally any NEURONS which are not motor or sensory. Interneurons may also refer to neurons whose AXONS remain within a particular brain region in contrast to projection neurons, which have axons projecting to other brain regions. Intercalated Neurons,Intercalated Neuron,Interneuron,Neuron, Intercalated,Neurons, Intercalated
D008959 Models, Neurological Theoretical representations that simulate the behavior or activity of the neurological system, processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment. Neurologic Models,Model, Neurological,Neurologic Model,Neurological Model,Neurological Models,Model, Neurologic,Models, Neurologic
D009435 Synaptic Transmission The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES. Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D011726 Pyridinium Compounds Derivatives of PYRIDINE containing a cation C5H5NH or radical C5H6N. Compounds, Pyridinium
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004705 Endocytosis Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis. Endocytoses
D005071 Evoked Potentials Electrical responses recorded from nerve, muscle, SENSORY RECEPTOR, or area of the CENTRAL NERVOUS SYSTEM following stimulation. They range from less than a microvolt to several microvolts. The evoked potential can be auditory (EVOKED POTENTIALS, AUDITORY), somatosensory (EVOKED POTENTIALS, SOMATOSENSORY), visual (EVOKED POTENTIALS, VISUAL), or motor (EVOKED POTENTIALS, MOTOR), or other modalities that have been reported. Event Related Potential,Event-Related Potentials,Evoked Potential,N100 Evoked Potential,P50 Evoked Potential,N1 Wave,N100 Evoked Potentials,N2 Wave,N200 Evoked Potentials,N3 Wave,N300 Evoked Potentials,N4 Wave,N400 Evoked Potentials,P2 Wave,P200 Evoked Potentials,P50 Evoked Potentials,P50 Wave,P600 Evoked Potentials,Potentials, Event-Related,Event Related Potentials,Event-Related Potential,Evoked Potential, N100,Evoked Potential, N200,Evoked Potential, N300,Evoked Potential, N400,Evoked Potential, P200,Evoked Potential, P50,Evoked Potential, P600,Evoked Potentials, N100,Evoked Potentials, N200,Evoked Potentials, N300,Evoked Potentials, N400,Evoked Potentials, P200,Evoked Potentials, P50,Evoked Potentials, P600,N1 Waves,N2 Waves,N200 Evoked Potential,N3 Waves,N300 Evoked Potential,N4 Waves,N400 Evoked Potential,P2 Waves,P200 Evoked Potential,P50 Waves,P600 Evoked Potential,Potential, Event Related,Potential, Event-Related,Potential, Evoked,Potentials, Event Related,Potentials, Evoked,Potentials, N400 Evoked,Related Potential, Event,Related Potentials, Event,Wave, N1,Wave, N2,Wave, N3,Wave, N4,Wave, P2,Wave, P50,Waves, N1,Waves, N2,Waves, N3,Waves, N4,Waves, P2,Waves, P50
D005089 Exocytosis Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the CELL MEMBRANE.

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