title: Temperature-dependent separation of a delayed-onset long-lasting enhancement mediated by coactivation of NMDA and metabotropic glutamate receptors following a transient exposure of extracellular high Ca(2+).
abstract: Transient increases in the concentration of extracellular Ca(2+) play an essential role in various physiological and/or pathological implications. Here the effect of low temperatures on synaptic transmission modulated by a brief increase in extracellular high Ca(2+) was studied in CA1 area of hippocampal slices from hamsters. A high Ca(2+) pulse (4.5 mM) induced a long-lasting enhancement at 25, 20, or 17 degrees C, but not at 15 degrees C. While the temperature was lowered to 17 degrees C, the overall expression of synaptic responses following a high Ca(2+) pulse was separated into two sequential enhanced components: an initial component (approximately 30-40 min in duration), followed by a delayed-onset component that was sustained throughout the remainder of the experiment. Application of 100 microM D-2-amino-5-phosphonovalerate, a selective antagonist of N-methyl-D-asparate receptors, or (RS)-alpha-Methyl-4-carboxyphenylglycine, a selective antagonist of metabotropic glutamate (mGlu) receptors, during a high Ca(2+) pulse at 17 degrees C blocked the development of the delayed-onset enhanced component without affecting the initial enhanced component significantly. In contrast, the application of D-2-amino-5-phosphonovalerate or (RS)-alpha-Methyl-4-carboxyphenylglycine immediately after a high Ca(2+) pulse at 17 degrees C had no discernible effects on the development of both components. These results indicate that low temperatures (e.g. 17 degrees C) unmasked two enhanced components that cannot be seen as separate components in the overall potentiation, while long-lasting enhancement was generated at higher temperatures (e.g. 25 degrees C). The development of the delayed-onset enhanced component primarily depended on coactivation of N-methyl-D-asparate and mGlu receptors during a high Ca(2+) challenge at 17 degrees C. The findings here may provide new understanding of the use of low temperatures and promise significant insight into a novel therapeutic intervention in the CNS while the glutamatergic signaling pathway is abnormally activated by certain ambient insults, such as transient increases in the concentration of extracellular Ca(2+).
authors.affiliation: Department of Physiology and Biophysics, National Defense Medical Center, 114, Taipei, Taiwan, People's Republic of China. snyang@ndmctsgh.edu.tw
authors.forename: S N
authors.initials: SN
authors.lastname: Yang
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D003080:Cold Temperature; D006224:Cricetinae; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008647:Mesocricetus; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013696:Temperature
chemical_list: D001565:Benzoates; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C079694:alpha-methyl-4-carboxyphenylglycine; D015763:2-Amino-5-phosphonovalerate; D002118:Calcium; D005998:Glycine