Abstract
A molecular-level theory is constructed for the control of fast neurotransmitter release, based on recent experimental findings that depolarization shifts presynaptic autoreceptors to a low affinity state and that an autoreceptor must be bound to a transmitter before it can become associated with the exocytotic apparatus. It is assumed that such an association blocks release; experimental support for this assumption is cited. The theory provides mechanisms for key experimental results concerning the essence of the matter, what controls the time course of evoked release? The same general model can account for both evoked and spontaneous release. The new theory can be regarded as a molecular implementation of the (phenomenological) calcium-voltage hypothesis that was suggested earlier.
Similar content being viewed by others
References
Arechiga, H., A. Cannone, H. Parnas and I. Parnas (1990). Blockage of synaptic release by brief hyperpolarizing pulses in the neuromuscular junction of the crayfish. J. Physiol. 430, 119–133.
Ashkenazy, G. and H. Parnas (1996). BIOQ Manual. Department of Neurobiology, The Hebrew University, Jerusalem, Israel. Home page: http://www.ls.huji.ac.il/∼parnas/Bioq/bioq.html
Augustine, G., M. Charlton and S. Smith (1987). Calcium action in synaptic transmitter release. Ann. Rev. Neurosci. 10, 633–693.
D’Agostino, G., H. Kilbinger, M. C. Chiari and F. Grana (1986). Presynaptic inhibitory muscarinic receptors modulating [3H]acetylcholine release in the rat urinary bladder. J. Pharmacol. Exp. Therapeutics 239, 522–528.
Dolezal, V. and S. Tucek (1993). Presynaptic muscarinic receptors and the release of acetylcholine from cerebrocortical prisms: role of Ca2+ and K+ concentrations. Naunun Schmiedebergs Arch. Pharmacol. 348, 228–233.
Geppert, M., Y. Goda, R. Hammer, T. Rozahl, C. Stevens and T. Sudnof (1994). Synaptotagmin I: a major Ca2+ sensor for transmitter release at a central synapse. Cell 79, 717–727.
Goda, Y. and C. Stevens (1994). Two components of transmitter release at a central synapse. Proc. Natl. Acad. Sci. USA 91, 12942–12946.
Hochner, B., H. Parnas and I. Parnas (1989). Membrane depolarization evokes neurotransmitter release in the absence of calcium entry. Nature 243, 433–435.
Ilouz, N., L. Branski, H. Parnas and M. Linial (1999). Depolarization affects the binding properties of mAChRs and their interaction with SNARE proteins. Submitted for publication.
Katz, B. and R. Miledi (1977). Transmitter leakage from motor nerve endings. Proc. R. Soc. (Lond.) B196, 59–72.
Khanin, R., H. Parnas and L. Segel (1997). ’First step’ negative feedback accounts for inhibition of fast neurotransmitter release. J. Theor. Biol. 188, 261–276.
Kloog, Y., R. Garlon and M. Sokolovsky (1986). Bisquaternary pyridinium oximes as presynaptic agonists and postsynaptic antagonists of muscarinic receptors. J. Neurochem. 46, 767–772.
Linial, M., N. Ilouz and H. Parnas (1997). Voltage-dependent interaction between the muscarinic ACh receptor and proteins of the exocytic machinery. J. Physiol. 504, 251–258.
Lovinger, D., E. Tyler, S. Fidler and A. Merritt (1993). Properties of a presynaptic metabotrpopic glutamate receptor in rat neosriatal slices. J. Neurophysiol. 69, 1236–1244.
Lustig, C. (1989). Neurotransmitter release: models and mechanisms, PhD thesis, Department of Applied Mathematics and Computer Science, The Weizmann Institute of Science, Rehovot, Israel.
Lustig, C., H. Parnas and L. Segel (1989). Neurotransmitter release: development of a theory for total release based on kinetics. J. Theor. Biol. 136, 151–170.
Lustig, C., H. Parnas and L. Segel (1990). Release kinetics as a tool to describe drug effects on neurotransmitter release. J. Theor. Biol. 144, 225–248.
Lynch, M. (1991). Presynaptic mechanisms in the maintenance of long-term potentiation: the role of arachidonic acid, in Excitatory Amino Acids and Synaptic Transmission, H. Wheal and A. Thomson (Eds), London: Academic Press.
Michaelson, D., S. Avissar, Y. Kloog and M. Sokolovsky (1979). Mechanism of acetylcholine release: possible involvement of presynaptic muscarinic receptors in regulation of acetylcholine release and protein phosporylation. Proc. Natl. Acad. Sci. USA 76, 6336–6340.
Morita, K., R. A. North and T. Tokimasa (1982). Muscarinic presynaptic inhibition of synaptic transmission in myenteric plexus of guinea-pig ileum. J. Physiol. 333, 141–149.
Parnas, H., J. Dudel and I. Parnas (1986). Neurotransmitter release and its facilitation in crayfish. VII. Another voltage-dependent process besides Ca-entry controls time course of phasic release. Pflügers Arch. 406, 121–130.
Parnas, H., G. Hovav and I. Parnas (1989). Effect of Ca2+ diffusion on the time course of neurotransmitter release. Biophys. J. 55, 859–874.
Parnas, H., M. Linial and I. Parnas (1997). The role of autoreceptors in initiation of release. Current Topics Pharmacol. 3, 177–191.
Parnas, H. and I. Parnas (1994). Neurotransmitter release at fast synapses. J. Membr. Biol. 142, 267–279.
Parnas, I., H. Parnas and J. Dudel (1986). Neurotransmitter release and its facilitation in cray-fish. VIII. Modulation of release by hyperpolarizing pulses. Pflügers Arch. 406, 131–137.
Parnas, H., I. Parnas, R. Ravin and B. Yudelevitch (1994). Glutamate and NMDA affect release from crayfish axon terminals in a voltage-dependent manner. Proc. Natl. Acad. Sci. USA 91, 11586–11590.
Peteris, A. and V. R. Ogren (1988). Interaction of forskolin with effect of atropine on [3H] acetylcholine secretion in guinea-pig ileum myenteric plexus. J. Physiol. 395, 441–453.
Ravin, R., M. Spira, H. Parnas and I. Parnas (1997). Simultaneous measurement of intracellular Ca2+ and asynchronous transmitter release from the same crayfish bouton. J. Physiol. 501, 251–262.
Silinsky, E. M. (1985). The biophysical pharmacology of calcium-dependent acetylcholine. Pharmacol. Rev. 37, 81–132.
Silinsky, E. M., R. S. Redman, R. Qiu, J. K. Hirsch, J. M. Hunt, C. S. Solsona, S. Alford and R. C. MacDonald (1995). Neurotransmitter release evoked by nerve impulses without Ca2+ entry through Ca2+ channels in frog motor nerve endings. J. Physiol. (Lond.) 482, 511–520.
Slutsky, I., H. Parnas and I. Parnas (1999). Presynaptic effects of muscarine on ACh release at the frog neuromuscular junction. J. Physiol. (Lond.), 514, 769–782.
Van der Kloot, W. and J. Molgó (1994). Quantal acetylcholine release at the vertebrate neuromuscular junction. Physiol. Rev. 74, 899–991.
Wessler, I. (1989). Control of transmitter release from the motor nerve by presynaptic nicotinic and muscarinic autoreceptors. TIPS 10, 110–114.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Yusim, K., Parnas, H. & Segel, L. Theory of fast neurotransmitter release control based on voltage-dependent interaction between autoreceptors and proteins of the exocytotic machinery. Bull. Math. Biol. 61, 701–725 (1999). https://doi.org/10.1006/bulm.1999.0107
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1006/bulm.1999.0107