Ultra-Fast Versus Sustained Cholinergic Transmission: A Variety of Different Mechanisms

Although synaptic transmission was assumed to use the same mechanisms in the case of different synapses of the central and peripheral nervous system, recent research revealed a great variety of different processes. Time might be a crucial factor to be considered in this diversity. It is recalled that the speed of a chemical reaction is inversely related to affinity. "Time is gained at the expense of sensitivity” as noticed by Bernard Katz (1989). Therefore, synaptic transmission will occur at a high speed only if it is supported by low affinity reactions. In the present work, we compare two examples of ultra-rapid transmission (the Torpedo nerve electroplaque synapse and the rat hippocampus mossy fiber/CA3 synapses), with a cholinergic process operating with high affinity but at a low speed: the release of glutamate elicited by nicotine from mossy fibers of the rat hippocampu

Contrôle présynaptique de la libération du glutamate par les fibres moussues de l'hippocampe de rat : zinc, canaux K[ATP] et neuroprotection

Nous avons étudié les régulations présynaptiques de la libération de glutamate (Glu) et leurs répercussions physiologiques et pathologiques. En utilisant des synaptosomes des fibres moussues de l'hippocampe, nous avons établi la relation entre potentiel de membrane et quantité de Glu libéré. La nicotine (1-25µM) déclenche la libération du Glu apparemment sans affecter le potentiel de membrane. Le zinc (1-20 µM) inhibe la libération de Glu en s'opposant à la dépolarisation des fibres moussues. En utilisant des cultures organotypiques d'hippocampe, nous avons démontré un effet neuroprotecteur du Zn suite à l'ischémie. Ceci résulte de son action inhibitrice sur la libération du Glu, conséquence de l'activation des canaux potassiques sensibles à l'ATP (K[ATP]). Nous avons analysé le site de liaison du Zn sur le K[ATP] et identifié les acides-aminés histidines H326 et H332, présents dans un secteur extracellulaire de la sous-unité SUR1, comme déterminants responsables de l'effet activateur

You don't believe in a patient's depression? Watch the watch!

Depressive states may at times be particularly tricky to ascertain or confirm during a time-limited consultation. For example, a patient may present with what has been termed as smiling depression. We present the case of a female patient with bipolar II disorder whose difficult-to-ascertain depression could be confirmed by her automatic wristwatch, which regularly stopped when she was hypokinetic as a result of her depression

Reconstitution of mediatophore-supported quantal acetylcholine release.

Synaptic transmission of a nerve impulse is an extremely rapid event relying on transfer of brief chemical impulses from one cell to another. This transmission is dependent upon Ca2+ and known to be quantal, which led to the widely accepted vesicular hypothesis of neurotransmitter release. However, at least in the case of rapid synaptic transmission the hypothesis has been found difficult to reconcile with a number of observations. In this article, we shall review data from experiments dealing with reconstitution of quantal and Ca2+-dependent acetylcholine release in: i) proteoliposomes, ii) Xenopus oocytes, and iii) release-deficient cell lines. In these three experimental models, release is dependent on the expression of the mediatophore, a protein isolated from the plasma membrane of cholinergic nerve terminals of the Torpedo electric organ. We shall discuss the role of mediatophore in quantal acetylcholine release, its possible involvement in morphological changes affecting presynaptic membrane during the release, and its interactions with others proteins of the cholinergic nerve terminal

Nicotine-induced and depolarisation-induced glutamate release from hippocampus mossy fibre synaptosomes: two distinct mechanisms

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 (EC(50) 3.14 microM; V(max) 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 microM) were similar to those of nicotine (25 microM). Nicotinic alpha7 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 Ca(2+) channels and (ii) a slower nicotinic activation which does not involve depolarisation or dissipation of the vesicular proton gradient

Predictors of short term treatment outcome in patients with achalasia following endoscopic or surgical therapy

Pneumatic balloon dilation and surgical myotomy are the most effective treatments for achalasia. While there is controversy which method is best, the aim of the current study was to identify predictors of symptom recurrence after endoscopic or surgical therapy