Is activation of metabotropic glutamate receptors responsible for acute hyposic changes in hippocampal neurons?
In whole-cell recordings from CA1 neurons in slices from rats, the mGLUR agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (ACPD; 10 microM) had a depolarizing action on most cells, associated with an increase in input resistance and suppression of afterhyperpolarizations. Under voltage-clamp, there were corresponding changes in membrane current and conductance; in the presence of ACPD, the slow voltage-dependent outward current recorded at approximately -25 mV was smaller and was more clearly depressed by hypoxia. Neither ACPD nor mGLUR antagonists, L(+)-2-amino-3-phosphonoproprionic acid (L-AP3; 1 mM) and (+)-alpha-methyl-4-carboxyphenyl-glycine (MCPG; 0.5 mM), reduced the hyperpolarization or outward current (or the associated changes in input resistance or conductance) induced by 2 min of hypoxia. Early inward currents, corresponding to the early, transient depolarizing effect of hypoxia, wer also not significantly depressed by either MCPG or L-AP3. The hypoxic responses of CA1 neurons in slices are therefore unlikely to be caused mainly be glutamate release and activation of mGLURs.
Erdemli
G
G
McGill University, Anaesthesia Research Department, Montreal, Que, Canada.
Krnjević
D000818:Animals; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects*
D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane