Ionic dysregulations typical of ischemia provoke release of glycine and GABA by multiple mechanisms.
Energy deprivation during ischemia causes dysregulations of ions, particularly sodium, potassium and calcium. Under these conditions, release of neurotransmitters is often enhanced and can occur by multiple mechanisms. The aim of this work was to characterize the modes of exit of glycine and GABA from nerve endings exposed to stimuli known to reproduce some of the ionic changes typical of ischemic conditions. Their approach was chosen instead of application of ischemic conditions because the release evoked during ischemia is mechanistically too heterogeneous. Mouse hippocampus and spinal cord synaptosomes, pre-labeled with [(3)H]glycine or [(3)H]GABA, were exposed in superfusion to 50 mM KCl or to 10 microM veratridine. The evoked overflows differed greatly between the two transmitters and between the two regions examined. Significant portions of the K(+)- and the veratridine-evoked overflows occurred by classical exocytosis. Carrier-mediated release of GABA, but not of glycine, was evoked by high K(+); GABA and, less so, glycine were released through transporter reversal by veratridine. External calcium-dependent overflows were only in part sensitive to omega-conotoxins; significant portions occurred following reversal of the plasmalemmal Na(+)/Ca(2+) exchanger. Finally, a relevant contribution to the overall transmitter overflows came from cytosolic calcium originating through the mitochondrial Na(+)/Ca(2+) exchanger. To conclude, ionic dysregulations typical of ischemia cause neurotransmitter release by heterogeneous mechanisms that differ depending on the transmitters and the CNS regions examined.
Department of Experimental Medicine, University of Genova, Genova, Italy.
Elisa
E
Luccini
Cristina
C
Romei
Silvia
S
Di Prisco
Maurizio
M
Raiteri
Luca
L
Raiteri
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D005998:Glycine / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D050479:Neurotransmitter Transport Proteins / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000187:drug effects / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014701:Veratridine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D050479:Neurotransmitter Transport Proteins; D019831:Sodium-Calcium Exchanger; D005680:gamma-Aminobutyric Acid; D011189:Potassium Chloride; D014701:Veratridine; D005998:Glycine