Relationships Among ATP Synthesis, K+ Gradients, and Neurotransmitter Amino Acid Levels in Isolated Rat Brain Synaptosomes
: Correlations were made among ATP synthesis, transmembrane K+ gradients, and leakage of three amino acid neurotransmitters, γ‐aminobutyric acid (GABA), aspartate, and glutamate, in rat brain synaptosomes incubated under normoxic and respiration‐limited conditions. Even under normoxic conditions, a...
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| Veröffentlicht in: | Journal of neurochemistry 1987-10, Vol.49 (4), p.1229-1240 |
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| creator | Dagani, Fiorenzo Erecinska, Maria |
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Correlations were made among ATP synthesis, transmembrane K+ gradients, and leakage of three amino acid neurotransmitters, γ‐aminobutyric acid (GABA), aspartate, and glutamate, in rat brain synaptosomes incubated under normoxic and respiration‐limited conditions. Even under normoxic conditions, a substantial proportion of total ATP synthesis (8%) was provided by glycolysis. Limitation of respiration by ∼30% through addition of amobarbital (Amytal) caused a twofold decrease in the cre‐atine phosphate/creatine ([CrP]/[Cr]) ratio, and consequently the [ATP]/[ADP] ratio, and a threefold increase in lactate production. There was a detectable decrease in intracellular [K+] and small rises in external GABA, aspartate, and glutamate concentrations. More severe limitations in ATP synthesis caused larger declines in the [CrP]/[Cr] ratio and progressive leakage of K+ and neurotransmitter amino acids. A comparison of ΔGATP and ΔGNa,k showed the former to be larger by 6 kcal, which indicates that the plasma membrane Na+/K+ pump operates at far from equilibrium. Under respiration‐limited conditions, even when total ATP synthesis decreased by ∼80% and [ATP] declined to |
| doi_str_mv | 10.1111/j.1471-4159.1987.tb10015.x |
| format | Article |
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Correlations were made among ATP synthesis, transmembrane K+ gradients, and leakage of three amino acid neurotransmitters, γ‐aminobutyric acid (GABA), aspartate, and glutamate, in rat brain synaptosomes incubated under normoxic and respiration‐limited conditions. Even under normoxic conditions, a substantial proportion of total ATP synthesis (8%) was provided by glycolysis. Limitation of respiration by ∼30% through addition of amobarbital (Amytal) caused a twofold decrease in the cre‐atine phosphate/creatine ([CrP]/[Cr]) ratio, and consequently the [ATP]/[ADP] ratio, and a threefold increase in lactate production. There was a detectable decrease in intracellular [K+] and small rises in external GABA, aspartate, and glutamate concentrations. More severe limitations in ATP synthesis caused larger declines in the [CrP]/[Cr] ratio and progressive leakage of K+ and neurotransmitter amino acids. A comparison of ΔGATP and ΔGNa,k showed the former to be larger by 6 kcal, which indicates that the plasma membrane Na+/K+ pump operates at far from equilibrium. Under respiration‐limited conditions, even when total ATP synthesis decreased by ∼80% and [ATP] declined to <0.4 mM ΔGATP was still larger than ΔGNa,k. It is suggested that during hypoxia and ischemia, the activity of the plasma membrane Na+/K+ pump in brain becomes limited by [ATP], which falls below the Am value for the low‐affinity regulatory site on the enzyme. This failure of the pump and consequent collapse of the ion gradients may contribute to the leakage of neurotransmitter amino acids that occurs in these pathological states.</description><identifier>ISSN: 0022-3042</identifier><identifier>EISSN: 1471-4159</identifier><identifier>DOI: 10.1111/j.1471-4159.1987.tb10015.x</identifier><identifier>PMID: 2442308</identifier><identifier>CODEN: JONRA9</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adenosine Triphosphate - biosynthesis ; Amino acid transmitters ; Amobarbital - pharmacology ; Animals ; Aspartic Acid - metabolism ; Biochemistry and metabolism ; Biological and medical sciences ; Brain - metabolism ; Central nervous system ; Energetics ; Energy Metabolism - drug effects ; Fundamental and applied biological sciences. Psychology ; gamma-Aminobutyric Acid - metabolism ; Glucose - pharmacology ; Glutamates - metabolism ; Glutamic Acid ; Hypoxia ; Ion Channels - metabolism ; Ischemia ; K+ gradients ; Male ; Neurotransmitter Agents - metabolism ; Oxygen Consumption - drug effects ; Potassium - metabolism ; Rats ; Rats, Inbred Strains ; Sodium - metabolism ; Synaptosomes - metabolism ; Vertebrates: nervous system and sense organs ; ynaptosomes</subject><ispartof>Journal of neurochemistry, 1987-10, Vol.49 (4), p.1229-1240</ispartof><rights>1988 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3999-6198beaa66713e8d080758782c71a9138502e3fa3377b1f1cabd628ab8b2601b3</citedby><cites>FETCH-LOGICAL-c3999-6198beaa66713e8d080758782c71a9138502e3fa3377b1f1cabd628ab8b2601b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1471-4159.1987.tb10015.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1471-4159.1987.tb10015.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27922,27923,45572,45573</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=7493211$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2442308$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dagani, Fiorenzo</creatorcontrib><creatorcontrib>Erecinska, Maria</creatorcontrib><title>Relationships Among ATP Synthesis, K+ Gradients, and Neurotransmitter Amino Acid Levels in Isolated Rat Brain Synaptosomes</title><title>Journal of neurochemistry</title><addtitle>J Neurochem</addtitle><description>:
Correlations were made among ATP synthesis, transmembrane K+ gradients, and leakage of three amino acid neurotransmitters, γ‐aminobutyric acid (GABA), aspartate, and glutamate, in rat brain synaptosomes incubated under normoxic and respiration‐limited conditions. Even under normoxic conditions, a substantial proportion of total ATP synthesis (8%) was provided by glycolysis. Limitation of respiration by ∼30% through addition of amobarbital (Amytal) caused a twofold decrease in the cre‐atine phosphate/creatine ([CrP]/[Cr]) ratio, and consequently the [ATP]/[ADP] ratio, and a threefold increase in lactate production. There was a detectable decrease in intracellular [K+] and small rises in external GABA, aspartate, and glutamate concentrations. More severe limitations in ATP synthesis caused larger declines in the [CrP]/[Cr] ratio and progressive leakage of K+ and neurotransmitter amino acids. A comparison of ΔGATP and ΔGNa,k showed the former to be larger by 6 kcal, which indicates that the plasma membrane Na+/K+ pump operates at far from equilibrium. Under respiration‐limited conditions, even when total ATP synthesis decreased by ∼80% and [ATP] declined to <0.4 mM ΔGATP was still larger than ΔGNa,k. It is suggested that during hypoxia and ischemia, the activity of the plasma membrane Na+/K+ pump in brain becomes limited by [ATP], which falls below the Am value for the low‐affinity regulatory site on the enzyme. This failure of the pump and consequent collapse of the ion gradients may contribute to the leakage of neurotransmitter amino acids that occurs in these pathological states.</description><subject>Adenosine Triphosphate - biosynthesis</subject><subject>Amino acid transmitters</subject><subject>Amobarbital - pharmacology</subject><subject>Animals</subject><subject>Aspartic Acid - metabolism</subject><subject>Biochemistry and metabolism</subject><subject>Biological and medical sciences</subject><subject>Brain - metabolism</subject><subject>Central nervous system</subject><subject>Energetics</subject><subject>Energy Metabolism - drug effects</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>gamma-Aminobutyric Acid - metabolism</subject><subject>Glucose - pharmacology</subject><subject>Glutamates - metabolism</subject><subject>Glutamic Acid</subject><subject>Hypoxia</subject><subject>Ion Channels - metabolism</subject><subject>Ischemia</subject><subject>K+ gradients</subject><subject>Male</subject><subject>Neurotransmitter Agents - metabolism</subject><subject>Oxygen Consumption - drug effects</subject><subject>Potassium - metabolism</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>Sodium - metabolism</subject><subject>Synaptosomes - metabolism</subject><subject>Vertebrates: nervous system and sense organs</subject><subject>ynaptosomes</subject><issn>0022-3042</issn><issn>1471-4159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1987</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkF1v0zAUhi0EGmXwE5AshLiBBB87jZPdoFLBGFQDjXFtOckpc5XExceFlV-Pq0a9xzeW_X4c-2HsBYgc0nq7yaHQkBUwr3OoK53HBoSAeX7_gM1O0kM2E0LKTIlCPmZPiDbJUxYlnLEzWRRSiWrG_t5gb6PzI925LfHF4MeffHH7jX_fj_EOydEb_uU1vwy2czjGdLJjx69xF3wMdqTBxYgh5dzo-aJ1HV_hb-yJu5FfkU_d2PEbG_n7YNNVarXb6MkPSE_Zo7XtCZ9N-zn78fHD7fJTtvp6ebVcrLJW1XWdlemHDVpblhoUVp2ohJ5XupKtBluDquZColpbpbRuYA2tbbpSVrapGlkKaNQ5e3Xs3Qb_a4cUzeCoxb63I_odGa1LXQKIZLw4GtvgiQKuzTa4wYa9AWEO4M3GHOiaA11zAG8m8OY-hZ9PU3bNgN0pOpFO-stJt9Tafp3gtY5ONl3USgIk27uj7Y_rcf8fDzCfr5cgZa3-ARSan7w</recordid><startdate>198710</startdate><enddate>198710</enddate><creator>Dagani, Fiorenzo</creator><creator>Erecinska, Maria</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>198710</creationdate><title>Relationships Among ATP Synthesis, K+ Gradients, and Neurotransmitter Amino Acid Levels in Isolated Rat Brain Synaptosomes</title><author>Dagani, Fiorenzo ; Erecinska, Maria</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3999-6198beaa66713e8d080758782c71a9138502e3fa3377b1f1cabd628ab8b2601b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1987</creationdate><topic>Adenosine Triphosphate - biosynthesis</topic><topic>Amino acid transmitters</topic><topic>Amobarbital - pharmacology</topic><topic>Animals</topic><topic>Aspartic Acid - metabolism</topic><topic>Biochemistry and metabolism</topic><topic>Biological and medical sciences</topic><topic>Brain - metabolism</topic><topic>Central nervous system</topic><topic>Energetics</topic><topic>Energy Metabolism - drug effects</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>gamma-Aminobutyric Acid - metabolism</topic><topic>Glucose - pharmacology</topic><topic>Glutamates - metabolism</topic><topic>Glutamic Acid</topic><topic>Hypoxia</topic><topic>Ion Channels - metabolism</topic><topic>Ischemia</topic><topic>K+ gradients</topic><topic>Male</topic><topic>Neurotransmitter Agents - metabolism</topic><topic>Oxygen Consumption - drug effects</topic><topic>Potassium - metabolism</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><topic>Sodium - metabolism</topic><topic>Synaptosomes - metabolism</topic><topic>Vertebrates: nervous system and sense organs</topic><topic>ynaptosomes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dagani, Fiorenzo</creatorcontrib><creatorcontrib>Erecinska, Maria</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neurochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dagani, Fiorenzo</au><au>Erecinska, Maria</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Relationships Among ATP Synthesis, K+ Gradients, and Neurotransmitter Amino Acid Levels in Isolated Rat Brain Synaptosomes</atitle><jtitle>Journal of neurochemistry</jtitle><addtitle>J Neurochem</addtitle><date>1987-10</date><risdate>1987</risdate><volume>49</volume><issue>4</issue><spage>1229</spage><epage>1240</epage><pages>1229-1240</pages><issn>0022-3042</issn><eissn>1471-4159</eissn><coden>JONRA9</coden><abstract>:
Correlations were made among ATP synthesis, transmembrane K+ gradients, and leakage of three amino acid neurotransmitters, γ‐aminobutyric acid (GABA), aspartate, and glutamate, in rat brain synaptosomes incubated under normoxic and respiration‐limited conditions. Even under normoxic conditions, a substantial proportion of total ATP synthesis (8%) was provided by glycolysis. Limitation of respiration by ∼30% through addition of amobarbital (Amytal) caused a twofold decrease in the cre‐atine phosphate/creatine ([CrP]/[Cr]) ratio, and consequently the [ATP]/[ADP] ratio, and a threefold increase in lactate production. There was a detectable decrease in intracellular [K+] and small rises in external GABA, aspartate, and glutamate concentrations. More severe limitations in ATP synthesis caused larger declines in the [CrP]/[Cr] ratio and progressive leakage of K+ and neurotransmitter amino acids. A comparison of ΔGATP and ΔGNa,k showed the former to be larger by 6 kcal, which indicates that the plasma membrane Na+/K+ pump operates at far from equilibrium. Under respiration‐limited conditions, even when total ATP synthesis decreased by ∼80% and [ATP] declined to <0.4 mM ΔGATP was still larger than ΔGNa,k. It is suggested that during hypoxia and ischemia, the activity of the plasma membrane Na+/K+ pump in brain becomes limited by [ATP], which falls below the Am value for the low‐affinity regulatory site on the enzyme. This failure of the pump and consequent collapse of the ion gradients may contribute to the leakage of neurotransmitter amino acids that occurs in these pathological states.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>2442308</pmid><doi>10.1111/j.1471-4159.1987.tb10015.x</doi><tpages>12</tpages></addata></record> |
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| subjects | Adenosine Triphosphate - biosynthesis Amino acid transmitters Amobarbital - pharmacology Animals Aspartic Acid - metabolism Biochemistry and metabolism Biological and medical sciences Brain - metabolism Central nervous system Energetics Energy Metabolism - drug effects Fundamental and applied biological sciences. Psychology gamma-Aminobutyric Acid - metabolism Glucose - pharmacology Glutamates - metabolism Glutamic Acid Hypoxia Ion Channels - metabolism Ischemia K+ gradients Male Neurotransmitter Agents - metabolism Oxygen Consumption - drug effects Potassium - metabolism Rats Rats, Inbred Strains Sodium - metabolism Synaptosomes - metabolism Vertebrates: nervous system and sense organs ynaptosomes |
| title | Relationships Among ATP Synthesis, K+ Gradients, and Neurotransmitter Amino Acid Levels in Isolated Rat Brain Synaptosomes |
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