Highlights from the Literature

Question: Do Mg2+ and Ca2+ work through functionally similar mechanisms to activate BK channels? Background: BK channels are large conductance Ca2+ and voltage-activated K+ channels, which allow K+ to leave the cytoplasm and promote membrane hyperpolarization under physiological conditions when activated by membrane potential and/or intracellular Ca2+. In addition to these two primary signals, BK channels are also sensitive to a number of regulatory ligands, including intracellular Mg2+. Previous studies suggest that Mg2+ and Ca2+ might work through functionally similar but independent mechanisms. This study examined the functional interaction between Mg2+and voltage-dependent activation of BK channels. Observations: Horrigan and Ma determined that the mechanism of Mg2+ action on BK channels is dependent on voltage sensor activation. They demonstrated that, when Mg2+ binds, it strengthens the allosteric coupling of voltage sensor activation to channel opening. Significance: These findings imply that intracellular Mg2+ activates BK channels through a fundamentally different mechanism from Ca2+. Intracellular Ca2+ promotes channel opening independent of voltage sensor activation. In contrast, intracellular Mg2+ has effects on opening and voltage sensor activation that are interdependent. In fact, the primary effect of Mg2+ on gating is to enhance voltage sensor/gate coupling such that open activated states are stabilized. Given that BK channels are important for the function of nerve, muscle, and secretory cells, these findings may have relevance to a number of physiologists. Requirement of inositol pyrophosphates for full exocytotic capacity in pancreatic cells. Illies C, Gromada J, Fiume R, Leibiger B, Yu J, Juhl K, Yang SN, Barma DK, Falck JR, Saiardi A, Barker CJ, Berggren PO. Science 318: 1299–1302, 2007.