PT  - JOURNAL ARTICLE
AU  - Lech Kiedrowski
TI  - Elevated Extracellular K<sup>+</sup> Concentrations Inhibit<em>N-</em>Methyl-<span class="sc">d</span>-Aspartate-Induced Ca<sup>2+</sup> Influx and Excitotoxicity
DP  - 1999 Oct 01
TA  - Molecular Pharmacology
PG  - 737--743
VI  - 56
IP  - 4
4099  - http://molpharm.aspetjournals.org/content/56/4/737.short
4100  - http://molpharm.aspetjournals.org/content/56/4/737.full
SO  - Mol Pharmacol1999 Oct 01; 56
AB  - Although extracellular [K+] ([K+]E) is highly elevated during brain ischemia, in vitro studies aimed at explaining the mechanisms of excitotoxicity have been conducted at low [K+]E. Whether high [K+]E affects excitotoxicity has not been formally addressed. Therefore this study, using digital fluorescence microscopy, tested how the elevation of [K+]Efrom 5.6 to 60 mM affectsN-methyl-d-aspartate (NMDA)-induced Ca2+ and Na+ influx, plasma membrane (PM) potential, mitochondrial Ca2+ load, and viability of primary cultures of rat cerebellar granule cells. High [K+]E curtailed the NMDA-induced Ca2+ and Na+ influx and mitochondrial Ca2+ overload, and prevented neuronal death. Surprisingly, the inhibitory effect of high [K+]E on the NMDA-induced Ca2+ influx could not be linked to depolarization of the PM. Apparently, the PM of cerebellar granule cells exposed to NMDA was more depolarized at low than at high [K+]E, probably because the NMDA-induced Na+ influx was greatly enhanced when the extracellular [Na+]/[K+] ratio was increased. When this ratio was small, i.e., at high [K+]E, the NMDA-induced increase in cytoplasmic [Na+] was suppressed, preventing Ca2+ influx via the reverse operation of the Na+/Ca2+ exchanger, which may explain the inhibitory effect of high [K+]Eon NMDA-induced Ca2+ influx and excitotoxicity. The American Society for Pharmacology and Experimental Therapeutics