IndraLab

Statements



reach
"Mg 2+ i activates BK channels by binding to low-affinity sites and can also modulate BK channel activity through inhibitory action on the high-affinity sites."

reach
"Our results show that intracellular Mg 2+ activates Slo1 BK channels through a fundamentally different mechanism from Ca 2+."

reach
"Intracellular Mg 2+ Enhances BK Channel Function at Physiological Conditions."

reach
"BK (Slo1) potassium channels are activated by millimolar intracellular Mg 2+ as well as micromolar Ca 2+ and membrane depolarization."

reach
"Fig. 5 A shows the comparison of Mg 2+ -dependent activation of the WT mSlo1 channels with that of mutant channels Q397R, Q397K, Q397D, Q397E, Q397C, and Q397W."

reach
"Moreover, in absence of Ca 2+ , BK channel-activating concentrations of Mg 2+ (10 mM) did not support CLR action."

reach
"Our results illustrate that Mg 2+ is coordinated at the interface between the VSD and the cytoplasmic domain to activate Slo1 BK channels."

reach
"The mechanism of Mg 2+ activation of the BK channel was thought to be due to a modulation of the voltage dependent BK channel activation XREF_BIBR, XREF_BIBR, XREF_BIBR."

reach
"Thus, for most alcoholics the low levels of internal Mg 2+ would contribute to tolerance of the EtOH induced potentiation of BK channel activity."

reach
"It has often been reported that Ca 2+ and Mg 2+ not only activate MaxiK channels but also block at millimolar concentrations."

reach
"In addition to Ca 2+, millimolar intracellular Mg 2+ can activate Slo1 channels."

reach
"The bound Mg 2+ at this narrow interdomain interface activates the BK channel through an electrostatic interaction with a positively charged residue in the VSD."

reach
"Thus, high concentrations of Ca 2+ and Mg 2+ may be acting at the same site (s) on the channel protein to modulate BK channel gating, independent of the action of Ca 2+ at the higher affinity, Ca 2+ -specific sites."

reach
"If we assume that high concentrations of Ca 2+ and Mg 2+ bind to the same or similar sites and are able to promote activation of Slo1 currents in a similar fashion, then the results in XREF_FIG A can be used to " subtract " the effect of Ca 2+ at the putative low affinity site from the V 0.5 -pCa relationship shown in XREF_FIG E."

reach
"The ability of Mg 2+ and other divalent cations to potentiate BK channel activation by Ca 2+ is associated with an increase in the Hill coefficient for activation by Ca 2+ (Golowasch et al. 1986; Oberhauser et al. 1988)."

reach
"In 2001, two independent studies of the cloned BK channel illustrated that millimolar Mg 2+ activates the BK channel via a low-affinity metal binding site that is independent from Ca 2+ dependent activation [XREF_BIBR, XREF_BIBR]."

reach
"Remarkably, this requirement was divalent-specific: in the absence of Ca , BK channel-activating concentrations of Mg (10 mM) did not support cholesterol-induced inhibition of BK current [69]."

reach
"Mg 2+, which enhances BK channel activation through the E399 low affinity site, only contributes to a slowing of deactivation of Slo1, with little effect on the activation kinetics of channel gating (XREF_FIG A)."

reach
"Additional support for a secondary site are the observations of Solaro et al. 1995 that cytoplasmic Mg 2+ modulates Ca 2+ -dependent activation of mSlo1 by binding to a low affinity site on the channel core, and the observations of Shi and Cui 2001 that Mg 2+ can increase BK channel activity under experimental conditions (1 mM Ca 2+ i), where the primary Ca 2+ binding sites would be saturated with Ca 2+ (Rothberg and Magleby 1999)."

reach
"Quantitative computation of these effects reveals that the overall effect of Mg 2+ under physiological conditions is to enhance BK channel function."