Raised extracellular potassium relieves the blockade by magnesium of NMDA-induced cerebellar cyclic GMP production.

In magnesium-containing Krebs buffer raised extracellular potassium increases the effects of NMDA on cyclic GMP production in immature rat cerebellar slices in vitro. This effect is not seen in magnesium-free buffer. The interaction between magnesium and potassium ions has competitive kinetics and the blockade of the NMDA channel by magnesium is surmountable by potassium. The inhibitory potency of magnesium on the NMDA receptor channel complex can thus be regulated by extracellular potassium levels. This may explain the unmasking of NMDA receptors in high frequency stimulation and their involvement in epilepsy and ischaemia, conditions in which synaptic potassium levels are elevated.