Proline-induced inhibition of glutamate release in hippocampal area CA1.
Concentrations of proline typical of human CSF have been shown to potentiate transmission at Schaffer collateral-commissural synapses on CA1 pyramidal cells of the rat hippocampus. This study tested the hypothesis that proline enhances excitatory synaptic transmission by increasing glutamate release. Two concentrations of proline were used: a concentration typical of normal human CSF (3 microM) and a concentration typical of CSF in persons with the genetic disorder hyperprolinemia type II (30 microM). Continuous exposure of hippocampal slices to either concentration of proline potentiated Schaffer collateral-commissural synaptic transmission. Proline shifted the plot of field EPSP slope against fiber volley amplitude upward. Contrary to the original hypothesis, neither concentration of proline reduced paired-pulse facilitation; 30 microM proline enhanced paired-pulse facilitation, whereas 3 microM proline had no effect. In line with its enhancement of paired-pulse facilitation, 30 microM proline reduced both the K+-evoked release of glutamate and aspartate from CA1 slices and the release of glutamate and aspartate from CA1 synaptosomes evoked by 4-aminopyridine. These results suggest that the proline-induced potentiation of Schaffer collateral-commissural synaptic transmission probably involves a postsynaptic, rather than a presynaptic, mechanism. Concentrations of proline normally found in human CSF little affect glutamate release. However, proline-induced inhibition of glutamate release may contribute to the neuropsychiatric disorders associated with hyperprolinemia type II.
Cohen
S M
SM
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710, USA.
Nadler
J V
JV
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D066298:In Vitro Techniques; D009994:Osmolar Concentration; D011188:Potassium / Q000494:pharmacology; D011392:Proline / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors
D018698:Glutamic Acid; D011392:Proline; D011188:Potassium