EXTRACELLULAR MG2+ REGULATES ACTIVATION OF RAT EAG POTASSIUM CHANNEL

The rat homologue of Drosophila ether a gogo cDNA (rat eag) encodes vo ltage-activated potassium (K) channels with distinct activation proper ties. Using the Xenopus expression system, we examined the importance of extracellular Mg2+ on the activation of rat eag. Extracellular Mg2 at physiological concentrations dramatically slowed the activation in a dose- and voltage-dependent manner. Other divalent cations exerted similar effects on the activation kinetics that correlated with their enthalpy of hydration. Lowering the external pH also resulted in a slo wing of the activation. Protons competed with Mg2+ as the effect of Mg 2+ was abolished at low pH. A kinetic model for rat eag activation was derived from the data indicating that all four channel subunits under go a Mg2+-dependent conformational transition prior to final channel a ctivation. The strong dependence of rat eag activation on both the res ting potential and the extracellular Mg2+ concentration constitutes a system for fine-tuning K channel availability in neuronal cells.