Depolarization by K+ and glutamate activates different neurotransmitter release mechanisms in gabaergic neurons: Vesicular versus non-vesicular release of GABA

doi:10.1016/0306-4522(93)90592-4

Neuroscience

Volume 54, Issue 4, June 1993, Pages 1019-1034

https://doi.org/10.1016/0306-4522(93)90592-4 Get rights and content

Abstract

Neurotransmitter release and changes in the concentration of intracellular free calcium ([Ca⁺⁺]_i) were studied in cultured GABAergic cerebral cortical neurons, from mice, upon depolarization with either an unphysiologicaLly high potassium concentration (55 mM) or the physiological excitatory neurotransmitter glutamate (100 μM). Both depolarizing stimuli exerted prompt increases in the release of preloaded [³H]GABA as well as in [Ca⁺⁺]_i. However, the basic properties of transmitter release and the increase in [Ca⁺⁺]_i, under a variety of conditions were different during stimulation with K⁺ or glutamate. Potassium-evoked release of [³H]GABA consisted of two phases, a rapid, large and transient phase followed by a smaller, more persistent second phase. The rapid phase was inhibited (60%) by nocodazole which reduced the number of vesicles in the neuntes by 80%. This rapid phase of the GABA release was also reduced by organic (verapamil) and inorganic (Co⁺⁺) Ca⁺⁺ channel blockers but was insensitive to the GABA transport inhibitor SKF 89976A. In contrast, the second phase was less sensitive to nocodazole and Ca⁺⁺ channel antagonists but could be inhibited by SKF 89976A. The glutamateinduced [³H]GABA release, which was mainly mediated by N-methyl-d-aspartate receptors, consisted of a single, sustained phase. This was insensitive to nocodazole, partly inhibited by verapamil and could be blocked by Co⁺⁺ as well as SKF 89976A. The action of Co⁺⁺ could be attributed to a block of N-methyl-d-aspartate-associated ion channels. These findings strongly suggest that the majority of the K⁺-stimulated GABA release is dependent upon vesicles whereas the glutamate induced release is non-vesicular and mediated by a depolarization-dependent reversal of the direction of high-affinity GABA transport. The basic differences in the mode of action of the two depolarizing stimuli were reflected in the properties of the increase in [Ca⁺⁺]_i elicited by 55 mM K⁺ and 100μM glutamate, respectively. The K⁺-induced increase in [Ca⁺⁺]_i was reduced by both verapamil and Ca⁺⁺-free media whereas the corresponding glutamate response was only sensitive to Ca⁺⁺-free conditions. Exposure of the cells to nocodazole or SKF 89976A had no effect on the ability of K⁺ or glutamate to increase [Ca⁺⁺]_i.

Altogether, the results clearly demonstrate that K⁺-induced transmitter release from these GABAergic neurons is vesicular in nature whereas that induced by the neurotransmitter glutamate is not.

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^†: Present address: Colorado State University, Department of Anatomy and Neurobiology, Anatomy Building, Fort Collings, CO 80523, U.S.A.

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Depolarization by K+ and glutamate activates different neurotransmitter release mechanisms in gabaergic neurons: Vesicular versus non-vesicular release of GABA

Abstract

Neurochem. Int.

Neuroscience

Neurochem. Int.

Int. J. devl Neurosci.

Epilepsy Res.

Int. J. devl Neurosci.

Brain Res.

Biochim. biophys. Acta

J. biol. Chem.

Neurochem. Int.

Adv. Biosci.

Eur. J. Pharmac.

Trends Neurosci.

J. biol. Chem.

Brain Res.

J. biol. Chem.

Neuroscience

Trends Neurosci.

Int. J. devl Neurosci.

Trends pharmac. Sci.

Brain Res.

Macromolecular sites for specific neuroioxins and drugs on chemosensitive synapses and electrical excitation in biological membranes

Ion Channels

Orally active and potent inhibitors of γ-aminobutyric acid uptake

J. med. Chem.

Toward a molecular understanding of synaptic transmitter release: Physiological clues from the squid giant synapse

Role for iontropic and metabotropic receptors in quisqualate-stimulated inositol polyphosphate accumulation in rat cerebral cortex

Molec. Pharmac.

Effects of inhibitors of protein synthesis and intracellular transport on the gamma-aminobutyric acid agonist-induced functional differentiation of cultured cerebellar granule cells

J. Neurochem.

3H-d-Aspartate release from cerebellargranule neurons is differentially regulated by glutamate, and K+-stimulation

J. Neurosci. Res.

Calcium-independent release of amino acid neurotransmitters: fact or artifact?

Prog. Neurobiol.

Glutamate mediates a slow synaptic response in hippocampal slice cultures

Calcium and transmitter release

Int. Rev. Neurobiol.

2-Amino-5-phosphonovalerate (2APV), a potent and selective antagonist of amino acid-induced and synaptic excitation

Neurosci. Lett.

On the site of origin of transmitter amino acids released by depolarization of nerve terminals in vitro

J. Neurochem.

The effects of methyl (2-thienyl-carbonyl)H-benzimidazolyl-2-carbamate, a new synthetic antitumoral drug interfering with microtubules, on mammalian cells cultured in vitro

Cancer Res.

Cooperative action of calcium ions in transmitter release at the neuromuscular junction

J. Physiol.

Excitatory amino acid-induced release of3H-GABA from cultured mouse cerebral cortex interneurons

J. Neurosci.

Stimulation of γ-[3H]-aminobutyric acid release from cultured mouse cerebral cortex neurons by sulphur-containing excitatory amino acid transmitter candidates: receptor activation mediates two distinct mechanisms of release

J. Neurochem.

Glutamate: a neurotransmitter in mammalian brain

J. Neurochem.

Dantrolene prevents glutamate cytotoxicity and Ca2+ release from intracellular stores in cultured cerebral cortical neurons

J. Neurochem.

Mobilization of dantrolene sensitive intracellular calcium pools is involved in the cytotoxicity induced by quisqualate and N-methyl-d-aspartate but not by 2-ammo-3-(3-hydroxy-5-methylisoxazol-4-yl)propionate) and kainate in cultured cerebral cortical neurons

Uptake of γ-aminobutyric acid by a synaptic vesicle fraction isolated from rat brain

J. Neurochem.

Comparison of the properties of gamma-aminobutyric acid andl-glutamate uptake into synaptic vesicles isolated from rat brain

J. Neurochem.

Expression of excitatory amino acid receptors by cerebellar cells of the type-2 astrocyte cell lineage

J. Neurochem.

GABA release triggered by the activation of neuron-Uke non-NMDA receptors in cultured type-2 astrocytes is carrier-mediated

Glia

Calcium antagonism and calcium entry blockade

Pharmac. Rev.

Glutamate receptor structure function

Depolarization by K⁺ and glutamate activates different neurotransmitter release mechanisms in gabaergic neurons: Vesicular versus non-vesicular release of GABA

³H-d-Aspartate release from cerebellargranule neurons is differentially regulated by glutamate, and K⁺-stimulation

Excitatory amino acid-induced release of³H-GABA from cultured mouse cerebral cortex interneurons

Stimulation of γ-[³H]-aminobutyric acid release from cultured mouse cerebral cortex neurons by sulphur-containing excitatory amino acid transmitter candidates: receptor activation mediates two distinct mechanisms of release

Dantrolene prevents glutamate cytotoxicity and Ca²⁺ release from intracellular stores in cultured cerebral cortical neurons