The present address of J. Miguel Cordeiro is the Lab. Farmacologia e Neurobiologia, ICBAS, Universidade do Porto, 4099-003 Porto, Portugal.
Nicotine-induced and depolarisation-induced glutamate release from hippocampus mossy fibre synaptosomes: two distinct mechanisms
Version of Record online: 15 MAY 2009
© 2009 The Authors. Journal Compilation © 2009 International Society for Neurochemistry
Journal of Neurochemistry
Volume 110, Issue 2, pages 570–580, July 2009
How to Cite
Bancila, V., Cordeiro, J. M., Bloc, A. and Dunant, Y. (2009), Nicotine-induced and depolarisation-induced glutamate release from hippocampus mossy fibre synaptosomes: two distinct mechanisms. Journal of Neurochemistry, 110: 570–580. doi: 10.1111/j.1471-4159.2009.06169.x
- Issue online: 25 JUN 2009
- Version of Record online: 15 MAY 2009
- Received March 2, 2009; accepted April 23, 2009.
- glutamate release;
- hippocampus mossy fibres;
- membrane potential;
- vesicular proton gradient
Hippocampus mossy fibre terminals activate CA3 pyramidal neurons via two distinct mechanisms, both quantal and glutamatergic: (i) rapid excitatory transmission in response to afferent action potentials and (ii) delayed and prolonged release following nicotinic receptor activation. These processes were analysed here using rat hippocampus mossy fibres synaptosomes. The relationships between synaptosome depolarisation and glutamate release were established in response to high-KCl and gramicidin challenges. Half-maximal release corresponded to a 52 mV depolarisation step. KCl-induced release was accompanied by transient dissipation of the proton gradient across synaptic vesicle membrane. Nicotine elicited a substantial glutamate release from mossy fibre synaptosomes (EC50 3.14 μM; Vmax 12.01 ± 2.1 nmol glutamate/mg protein; Hill’s coefficient 0.99). However, nicotine-induced glutamate release was not accompanied by any change in the membrane potential or in the vesicular proton gradient. The effects of acetylcholine (200 μM) were similar to those of nicotine (25 μM). Nicotinic α7 receptors were evidenced by immuno-cytochemistry on the mossy fibre synaptosome plasma membrane. Therefore, the same terminals can release glutamate in response to two distinct stimuli: (i) rapid neurotransmission involving depolarisation-induced activation of voltage-gated Ca2+ channels and (ii) a slower nicotinic activation which does not involve depolarisation or dissipation of the vesicular proton gradient.