The synapsins: beyond the regulation of neurotransmitter release

The synapsins are a family of five closely related neuron-specific phosphoproteins associated with the membranes of synaptic vesicles. The synapsins have been implicated in the regulation of neurotransmitter release. They tether synaptic vesicles to actin filaments in a phosphorylation-dependent manner, controlling the number of vesicles available for release at the nerve terminus. A growing body of evidence suggests that the synapsins play a broad role during neuronal development. They participate in the formation and maintenance of synaptic contacts among central neurons. In addition, each synapsin has a specific role during the elongation of undifferentiated processes and their posterior differentiation into axons and dendrites. In this review, we focus on these novel roles of synapsins during the early stages of development. Received 26 September 2001; received after revision 8 November 2001; accepted 9 November 2001     

Depression of spontaneous and ionophore-induced neurotransmitter release by Salmonella.

Exposure of frog neuromuscular junctions to heat-killed, lyophilized Salmonella typhimurium (SR 11) produces an early increase in spontaneous transmitter release followed by depression of release and blockade of the obligatory release usually induced by ionophore X537A.     

Depression of spontaneous and ionophore-induced neurotransmitter release bySalmonella

Summary Exposure of frog neuromuscular junctions to heat-killed, lyophilizedSalmonella typhimurium (SR 11) produces an early increase in spontaneous transmitter release followed by depression of release and blockade of the obligatory release usually induced by ionophore X537A.This study was supported by the Office of Naval Research, Biophysics Section, NR 202-160, N00014-77-C-0630. X537A was a gift of Hoffman-LaRoche. I am greatly indebted to Dr R. McCallum for preparing the Salmonella material. J.A. Kuhn provided the technical assistance.     

Temperature dependence of neurotransmitter release in the antarctic fishPagothenia borchgrevinki

Summary The quantal contents of endplate potentials from extraocular muscles of an antarctic fishPagothenia borchgrevinki were measured over a range of temperatures. Quantal release was maximal at about 5°C but showed little dependence on temperature between –2°C and 10°C. Above 10°C quantal content declined until release ceased about 18°C. In view of the fact that the ambient temperature at which these fish live is constant at –1.9°C, the results suggest thatPagothenia borchgrevinki is only partially adapted to its environment despite 25 million years acclimatization.The authors wish to thank the staff of New Zealand's Scott Base, Antarctica, without whose cooperation the work would have been impossible. Mr J. Quinn of the Auckland University Physiology Department gave invaluable assistance with computing and electronics and the Antarctic Division of the New Zealand Department of Scientific and Industrial Research provided transportation and logistic support. The project was financially supported by the New Zealand University Grants Committee and the Auckland University Research Committee. S.P. was a Senior Fellow of the N.Z. Medical Research Council.     

Temperature dependence of neurotransmitter release in the antarctic fish Pagothenia borchgrevinki

The quantal contents of endplate potentials from extraocular muscles of an antarctic fish Pagothenia borchgrevinki were measured over a range of temperatures. Quantal release was maximal at about 5 degrees C but showed little dependence on temperature between -2 degrees C and 10 degrees C. Above 10 degrees C quantal content declined until release ceased about 18 degrees C. In view of the fact that the ambient temperature at which these fish live is constant at -1.9 degrees C, the results suggest that Pagothenia borchgrevinki is only partially adapted to its environment despite 25 million years acclimatization.     

Role of neurotransmitter release and cyclic AMP-dependent membrane phosphorylation in low voltage myocardial automaticity

Low voltage myocardial automaticity (LVA) was investigated by pharmacological modulations of the presynaptic and postsynaptic processes. The sensitivity of LVA both to inhibitor and stimulator of neurotransmitter release suggests its involvement in LVA genesis. Moreover, LVA is blocked by the inhibition of the cyclic AMP system, supporting the participation of the c-AMP-dependent membrane phosphorylation in calcium-mediated cardiac electrogenesis.     

Role of neurotransmitter release and cyclic AMP-dependent membrane phosphorylation in low voltage myocardial automaticity

Summary Low voltage myocardial automaticity (LVA) was investigated by pharmacological modulations of the presynaptic and postsynaptic processes. The sensitivity of LVA both to inhibitor and stimulator of neutrotransmitter release suggests its involvement in LVA genesis. Moreover, LVA is blocked by the inhibition of the cyclic AMP system, supporting the participation of the c-AMP-dependent membrane phosphorylation in calcium-mediated cardiac electrogenesis.Acknowledgment. The generous gift of RM1 12330A from Prof. G. Guellen, Paris, and of tolbutamide from Prof. T. Hayakawa, Tokyo, are gratefully acknowledged.     

The antagonism of adrenergic blockade by dichloroisoproterenol (DCI)

Zusammenfassung Mit Dibenzylin vorbehandelte anästhetisierte Hunde reagierten nach Dichloroisoproterenol(DCI)-Verabreichung sofort mit «Pressor response» auf Epinephrin und Norepinephrin. Ähnliche Befunde ergaben sich auch bei adrenergischer Blockade mittels Dihydroergotamin oder Benzodioxan.

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This study was supported in part by a Research Training Grant from the National Institutes of Health.     

The membrane domain of vacuolar H<Superscript>+</Superscript>ATPase: a crucial player in neurotransmitter exocytotic release

V-ATPases are multimeric enzymes made of two sectors, a V1 catalytic domain and a V0 membrane domain. They accumulate protons in various intracellular organelles. Acidification of synaptic vesicles by V-ATPase energizes the accumulation of neurotransmitters in these storage organelles and is therefore required for efficient synaptic transmission. In addition to this well-accepted role, functional studies have unraveled additional hidden roles of V0 in neurotransmitter exocytosis that are independent of the transport of protons. V0 interacts with SNAREs and calmodulin, and perturbing these interactions affects neurotransmitter release. Here, we discuss these data in relation with previous results obtained in reconstituted membranes and on yeast vacuole fusion. We propose that V0 could be a sensor of intra-vesicular pH that controls the exocytotic machinery, probably regulating SNARE complex assembly during the synaptic vesicle priming step, and that, during the membrane fusion step, V0 might favor lipid mixing and fusion pore stability.     

Inhibition by tetanus and botulinum A toxin of the release of [3H]noradrenaline and [3H]GABA from rat brain homogenate

Rat brain homogenate was preloaded with [3H]noradrenaline or [3H]GABA and stimulated with high K+. Tetanus toxin and botulinum A neurotoxin partially prevent the evoked [3H]noradrenaline release in the same range of toxin concentrations starting below 10(-10) M. In contrast, release of gamma-amino butyric acid (GABA) is much more sensitive to tetanus than to botulinum A toxin.     

Inhibition by tetanus and botulinum A toxin of the release of [3H]noradrenaline and [3H]GABA from rat brain homogenate

Summary Rat brain homogenate was preloaded with [³H]noradrenaline or [³H]GABA and stimulated with high K⁺. Tetanus toxin and botulinum A neurotoxin partially prevent the evoked [³H]noradrenaline release in the same range of toxin concentrations starting below 10^–10M. In contrast, release of -amino butyric acid (GABA) is much more sensitive to tetanus than to botulinum A toxin.     

Modification of the action of pentagastrin on acid secretion by botulinum toxin

Summary I.v. botulinum toxin after 60–90 min abolished the dose-response relationship between pentagastrin and gastric acid secretion in anesthetized rats and guinea-pigs. The toxin reduced but did not abolish the acid stimulatory effect of histamine. As expected, the acid response to vagal stimulation was abolished and that to methacholine in rats was unaltered by the toxin.Acknowledgment. We are grateful to the generosity of Dr Edward J. Schantz, Food Research Institute, University of Wisconsin, for the botulinum toxin used. — This research was supported by NIH grant 1 RO1 AM 17125, The Secretion of Pepsin.     

The potent tremorgenic neurotoxins lolitrem B and aflatrem: A comparison of the tremor response in mice

Summary Tremor dose-response curves were determined for mice dosed with the ryegrass neurotoxin lolitrem B, and the tremorgenic mycotoxin aflatrem. A family of characteristic curves was revealed for each tremorgen, with lolitrem B eliciting a sustained tremor response persisting for over 24 h.     

Modification of the action of pentagastrin on acid secretion by botulinum toxin.

I.v botulinum toxin after 60-90 min abolished the dose-response relationship between pentagastrin and gastric acid secretion in anesthetized rats and guinea-pigs. The toxin reduced but did not abolish the acid stimulatory effect of histamine. As expected, the acid response to vagal stimulation was abolished and that to methacholine in rats was unaltered by the toxin.     

Selective blockade by mephentermine of reserpine-induced serotonin depletion

Zusammenfassung Die kombinierte i.v. Verabreichung von Reserpin (1 mg/kg) und Mephentermin (1 mg/kg) bewirkte Erregung in Kaninchen. Diese Erregung ist verbunden mit einem Verlust an Noradrenalin (NE) im Gehirn, nicht jedoch mit einem Verlust an Serotonin (5-HT). Aus den Ergebnissen lässt sich schliessen, dass die beobachtete Erregung von einem momentanen Ungleichgewicht zwischen NE und 5-HT im Gehirn herrührt.

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This study is supported in part by Career Development Award No. K3 NB 15279-09 and Grant No. MH 11189 from the National Institutes of Health, U.S.P.H.S. The authors wish to thank Dr.A. J. Plummer of CIBA Pharmaceutical Company for supplying the reserpine phosphate and Dr.R. J. Bower of Wyeth Laboratories for the mephentermine used in this study.     

The potent tremorgenic neurotoxins lolitrem B and aflatrem: a comparison of the tremor response in mice

Tremor dose-response curves were determined for mice dosed with the ryegrass neurotoxin lolitrem B, and the tremor-genic mycotoxin aflatrem. A family of characteristic curves was revealed for each tremorgenic, with lolitrem B eliciting a sustained tremor response persisting for over 24 h.     

The release of dopamine from the putamen

Zusammenfassung Der Ruheertrag des Dopamins aus dem erregten Katzenputamen wurde bei genügender Niederfrequenzreizung der Substantia nigra mehr als verdoppelt. Mit dieser Beobachtung wird der histochemische Nachweis des nigro-neostriatalen dopaminergischen Weges gestützt.

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This work was supported by the Medical Research Council of Canada. Thanks are due toR. Walker for his excellent assistance.