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Inhibition of Calcium‐Dependent NMDA Receptor Current Rundown by Calbindin‐D 28k
Author(s) -
Price Christopher J.,
Rintoul Gordon L.,
Baimbridge Kenneth G.,
Raymond Lynn A.
Publication year - 1999
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.1471-4159.1999.0720634.x
Subject(s) - nmda receptor , calcium , calcium in biology , calbindin , microbiology and biotechnology , transfection , biology , receptor , chemistry , voltage dependent calcium channel , biophysics , intracellular , endocrinology , medicine , biochemistry , organic chemistry , gene
: NMDA receptors are regulated by several differentcalcium‐dependent processes. To determine if the presence of the intracellularcalcium‐binding protein calbindin‐D 28k can influence the calcium regulation of NMDA receptor activity,human embryonic kidney 293 cells were co‐transfected with cDNAs for NMDA receptor subunits and cablinding. Recordings were made using the nystatin perforated patch technique to preserve intracellular contents. When compared with control cells (transfected with cDNA enconding β‐galactosidase in place of calbindin), the presence of calbindin had no effect on either calcium‐dependent inactivation or the calciumsensitive, time‐dependent increase in glycine‐independent desensitization of NMDA receptor‐mediated currents. However, the development of calcium‐dependent rundown of peak glutamate‐evoked current was slowed significantly in calbindin versus β‐galactosidase cotransfected cells. This result was true for cells transfected with either NR1/NR2A or NR1/NR2B subunits, although calbindin was relatively less effective at inhibiting rundown in NR1/NR2B‐expressing cells. NMDA peak current rundown has been attributed to calcium‐induced depolymerization of the actin cytoskeleton. Therefore, our results indicate that although calbindin may not influence calcium‐dependent regulatory processes occurring very near the NMDA receptor channel, it appears to be more effective at buffering local elevations in intracellular calcium at the actin cytoskeleton.