Abstract
The soma, dendrites and axon of neurons may display calcium-dependent release of transmitters and peptides. Such release is named extrasynaptic for occurring in absence of synaptic structures. This review describes the cooperative actions of three calcium sources on somatic exocytosis. Emphasis is given to the somatic release of serotonin by the classical leech Retzius neuron, which has allowed detailed studies on the fine steps from excitation to exocytosis. Trains of action potentials induce transmembrane calcium entry through L-type channels. For action potential frequencies above 5 Hz, summation of calcium transients on individual action potentials activates the second calcium source: ryanodine receptors produce calcium-induced calcium release. The resulting calcium tsunami activates mitochondrial ATP synthesis to fuel transport of vesicles to the plasma membrane. Serotonin that is released maintains a large-scale exocytosis by activating the third calcium source: serotonin autoreceptors coupled to phospholipase C promote IP3 production. Activated IP3 receptors in peripheral endoplasmic reticulum release calcium that promotes vesicle fusion. The Swiss-clock workings of the machinery for somatic exocytosis has a striking disadvantage. The essential calcium-releasing endoplasmic reticulum near the plasma membrane hinders the vesicle transport, drastically reducing the thermodynamic efficiency of the ATP expenses and elevating the energy cost of release.
Highlights
The soma, dendrites and axon of neurons may display calcium-dependent release of transmitters and peptides
This review summarizes experimental evidence about the ways by which calcium flow through transmembrane and intracellular channels contributes in an orderly manner to induce vesicle transport and a large-scale exocytosis that lasts for hundreds of seconds
Somatic exocytosis by Retzius neurons is regulated by a sequential activation of three calcium sources
Summary
Streams of action potentials or long depolarizations may evoke calcium-dependent exocytosis of transmitters and peptides from the soma, dendrites and axon of neurons in the absence of pre- and postsynaptic structures [1,2,3,4,5,6,7,8]. Bursts of electrical activity or long depolarizations and calcium entry are needed to mobilize vesicles to the plasma membrane [21,22]. The injection of brief depolarizing current pulses through a microelectrode to produce trains of action potentials at 1 Hz trains (Figure 1), a frequency similar to that of spontaneous firing in serotonergic and other monoaminergic neurons [27,28,29,30], fails to promote any vesicle mobilization to the plasma membrane and exocytosis. Our laboratory has found that after 20 Hz stimulation in the presence of extracellular magnesium to block transmembrane calcium entry, vesicles remain at resting positions (Del Pozo-Sánchez, V., Mendez, B. and De-Miguel, F.F., in preparation)
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