Regulation of carrier-mediated and exocytotic release of [3H]GABA in rat brain synaptosomes. 1991

C M Carvalho, and C Bandeira-Duarte, and I L Ferreira, and A P Carvalho
Departamento de Zoologia, Universidade de Coimbra, Portugal.

In this study we investigated the role of external monovalent cations, and of intracellular Ca2+ concentration ([Ca2+]i) in polarized and depolarized rat cerebral cortex synaptosomes on the release of [3H]-gamma-aminobutyric acid (3H-GABA). We found that potassium-depolarization, in the absence of Ca2+, of synaptosomes loaded with 3H-GABA releases 7.4 +/- 2.1% of the accumulated neurotransmitter, provided that the external medium contains Na+, and an additional 19.0 +/- 2.5% is released upon adding 1.0 mM CaCl2 to the exterior. The Ca(2+)-independent release component does not occur in a choline medium and it is only 3.4 +/- 0.8% of the 3H-GABA accumulated in a Li+ medium, but both ions support the Ca(2+)-dependent release of 3H-GABA (13.4 +/- 0.6% in choline and 15.4 +/- 1.5% in Li+), which suggests that the exocytotic release is independent of the external monovalent cation present, whereas the carrier-mediated release specifically requires Na+ outside. Furthermore, previous release of the cytosolic 3H-GABA due to predepolarization in the absence of Ca2+ does not influence the amount of 3H-GABA subsequently released by exocytosis due to Ca2+ addition (19.1 +/- 2.5% or 19.1 +/- 1.1%, respectively). In choline or Li+ medium, the value of the [Ca2+]i is raised by Na+/Ca2+ exchange to 663 +/- 75 nM or 782 +/- 54 nM, respectively, within three minutes after adding 1.0 mM Ca2+, in the absence of depolarization, and parallel release experiments show no release of 3H-GABA in the choline medium, but a substantial release (7.1 +/- 2.1%) of 3H-GABA occurs in the Li+ medium without depolarization. Subsequent K(+)-depolarization shows normal Ca(2+)-dependent release of 3H-GABA in the choline medium (14.1 +/- 2.0%) but only 8.6 +/- 1.1% release in the Li+ medium, which suggests that raising the [Ca2+]i by Na+/Ca2+ exchange, without depolarization, supports some exocytotic release in Li+, but not in choline media. The role of [Ca2+]i and of membrane depolarization in the release process is discussed on the basis of the results obtained and other relevant observations which suggest that both Ca2+ and depolarization are essential for optimal exocytotic release of GABA.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D011188 Potassium An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002414 Cations, Monovalent Positively charged atoms, radicals or group of atoms with a valence of plus 1, which travel to the cathode or negative pole during electrolysis. Monovalent Cation,Cation, Monovalent,Monovalent Cations
D002540 Cerebral Cortex The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions. Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D005089 Exocytosis Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the CELL MEMBRANE.
D005680 gamma-Aminobutyric Acid The most common inhibitory neurotransmitter in the central nervous system. 4-Aminobutyric Acid,GABA,4-Aminobutanoic Acid,Aminalon,Aminalone,Gammalon,Lithium GABA,gamma-Aminobutyric Acid, Calcium Salt (2:1),gamma-Aminobutyric Acid, Hydrochloride,gamma-Aminobutyric Acid, Monolithium Salt,gamma-Aminobutyric Acid, Monosodium Salt,gamma-Aminobutyric Acid, Zinc Salt (2:1),4 Aminobutanoic Acid,4 Aminobutyric Acid,Acid, Hydrochloride gamma-Aminobutyric,GABA, Lithium,Hydrochloride gamma-Aminobutyric Acid,gamma Aminobutyric Acid,gamma Aminobutyric Acid, Hydrochloride,gamma Aminobutyric Acid, Monolithium Salt,gamma Aminobutyric Acid, Monosodium Salt
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013574 Synaptosomes Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates. Synaptosome

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