Extracellular Mg2+ regulates activation of rat eag potassium channel.
The rat homologue of Drosophila ether à gogo cDNA (rat eag) encodes voltage-activated potassium (K) channels with distinct activation properties. 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 slowing of the activation. Protons competed with Mg2+ as the effect of Mg2+ was abolished at low pH. A kinetic model for rat eag activation was derived from the data indicating that all four channel subunits undergo a Mg2+-dependent conformational transition prior to final channel activation. The strong dependence of rat eag activation on both the resting potential and the extracellular Mg2+ concentration constitutes a system for fine-tuning K channel availability in neuronal cells.
Terlau
H
H
Max-Planck-Institut für experimentelle Medizin, Abteilung Molekulare Biologie neuronaler Signale, Hermann-Rein-Strasse 3, D-37075 Göttingen, Germany.
Ludwig
J
J
Steffan
R
R
Pongs
O
O
Stühmer
W
W
Heinemann
S H
SH
D000818:Animals; D002413:Cations, Divalent / Q000494:pharmacology; D004594:Electrophysiology; D051638:Ether-A-Go-Go Potassium Channels; D005110:Extracellular Space / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008274:Magnesium / Q000502:physiology*; D009865:Oocytes; D009994:Osmolar Concentration; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats / Q000378:metabolism*; D013997:Time Factors; D014982:Xenopus laevis
D002413:Cations, Divalent; D051638:Ether-A-Go-Go Potassium Channels; D015221:Potassium Channels; D008274:Magnesium