Premium
NAAG and NAALADase influence NMDA receptor activation and axon‐to‐glia signalling in crayfish medial giant nerve fibers
Author(s) -
Urazaev, A. K.,
Gafurov B. S.,
Grossfeld R. M.,
Lieberman E. M.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.12_7.x
Subject(s) - nmda receptor , hyperpolarization (physics) , neuroscience , ampa receptor , depolarization , chemistry , glutamate receptor , metabotropic glutamate receptor , kainate receptor , biophysics , biology , receptor , biochemistry , organic chemistry , nuclear magnetic resonance spectroscopy
Action potential generation in crayfish giant nerve fibers causes a transient depolarization followed by a prolonged hyperpolarization in their associated glial cells. The glial potential changes, involving a nicotinic acetylcholine receptor (nAChR)‐induced decrease in Cl – permeability, are caused by axonal release of N‐acetylaspartylglutamate (NAAG) acting specifically on glial group II metabotropic glutamate (mGLUR II ). In addition, GLU formed by NAAG hydrolysis by NAALADase acts on NMDARs as well as mGLURs. Application of NMDA or l ‐aspartate also produces glial cell hyperpolarization that can be inhibited by antagonists of NMDA receptors (MK801) but not by antagonists of AMPA/kainate (AP4) or mGLURs (EGLU). Reducing extracellular Ca 2+ depresses the NMDA effect while Na + depletion, block of voltage‐dependent Ca 2+ channels (verapamil) or the nAChR (d‐tubocurarin) completely prevent the response to NMDA. The hyperpolarization caused by high frequency stimulation of the nerve fiber is only partially reduced by NMDAR blockade suggesting these receptors are not solely responsible for initiating the glial hyperpolarization under physiological conditions. These results also indicate that the transient depolarization, induced by physiological activation of glial NMDARs, opens voltage‐sensitive Ca 2+ channels leading to Ca 2+ influx. An increase in [Ca 2+ ] i by this mechanism potentiates the ACh release due to mGLUR II activation and the subsequent hyperpolarization mediated by the nAChR. Acknowledgements: Supported by NIH grant NS34799 and Guilford Pharmaceuticals, Baltimore, MD, USA.