Intracellular Mg(2+) enhances the function of BK-type Ca(2+)-activated K(+) channels.
BK channels modulate neurotransmitter release due to their activation by voltage and Ca(2+). Intracellular Mg(2+) also modulates BK channels in multiple ways with opposite effects on channel function. Previous single-channel studies have shown that Mg(2+) blocks the pore of BK channels in a voltage-dependent manner. We have confirmed this result by studying macroscopic currents of the mslo1 channel. We find that Mg(2+) activates mslo1 BK channels independently of Ca(2+) and voltage by preferentially binding to their open conformation. The mslo3 channel, which lacks Ca(2+) binding sites in the tail, is not activated by Mg(2+). However, coexpression of the mslo1 core and mslo3 tail produces channels with Mg(2+) sensitivity similar to mslo1 channels, indicating that Mg(2+) sites differ from Ca(2+) sites. We discovered that Mg(2+) also binds to Ca(2+) sites and competitively inhibits Ca(2+)-dependent activation. Quantitative computation of these effects reveals that the overall effect of Mg(2+) under physiological conditions is to enhance BK channel function.
Shi
J
J
Cardiac Bioelectricity Research and Training Center, Case Western Reserve University, Cleveland, OH 44106-7207, USA.
Cui
J
J
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000493:pharmacokinetics / Q000494:pharmacology; D003593:Cytoplasm / Q000737:chemistry; D004594:Electrophysiology; D015640:Ion Channel Gating / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008274:Magnesium / Q000493:pharmacokinetics / Q000494:pharmacology*; D009865:Oocytes / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated; D014982:Xenopus laevis
D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D008274:Magnesium; D002118:Calcium