IndraLab

Statements


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"Increased activity of BK channels caused by a mutation in the beta4 BK channel auxiliary subunit increases high-frequency firing and leads to temporal lobe seizures."

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"Although it is appreciated that some mechanisms of desensitization may depend on the co-expression of subunits with the subunit that forms the pore XREF_BIBR, XREF_BIBR, a BK channel in close proximity with a inactivating source would produce BK inactivation."

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"XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR On the other hand, well established (such as NS1608, NS8 and NS1619) and novel (such as NS11021) BK channel openers increase BK channel open probability and whole-cell BK currents, causing DSM hyperpolarization and relaxation in various species."

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"LRRC26 knockdown did not alter Ca 2+ sparks, but reduced BK channel voltage-sensitivity, which reduced channel apparent Ca 2+ -sensitivity and transient BK current frequency and amplitude in myocytes."

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"Compartment specific expression of beta subunits of the BK channel has been proposed to underlie differences in BK alcohol sensitivity between the somatic, dendritic and terminal compartments of neurons [XREF_BIBR]."

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"Paxilline, a specific BK channel blocker, blocks BK channels both intra- and extracellularly XREF_BIBR - XREF_BIBR."

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"In pursuing this idea we noted that it has been shown that two BK channel beta subunits (beta2 and beta3) produce BK inactivation by inserting their cytoplasmic N-terminal domains into the a subunit in such a way as to inhibit ion flow through the pore."

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"In the presence of BAPTA-AM, the BK channel modulators NS1619 and 12,14-dichlorodehydroabietic acid increased the BK current at concentrations of 10muM or more showing clear concentration dependency, whereas in its absence, the effect of both compounds was detected only at 30muM."

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"Taking these data together, the changes in BK current establish that the N999S mutation confers GOF properties to a brain expressed BK channel variant, producing larger BK currents that activate at lower voltages because of the shifted V 1/2 and activate faster and deactivate slower than WT."

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"In a patient affected by severe mental deficiency and autism (but not epilepsy), physical disruption of the KCNMA1 gene by chromosomal translocation led to haploinsufficiency and decreased BK currents in lymphoblastoid cell lines."

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"ANG II mediated BK channel degradation reduced BK currents in isolated myocytes and functional responses to iberiotoxin, a BK channel blocker, and NS1619, a BK activator, in pressurized (60 mmHg) cerebral arteries."

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"BK channels with slightly different biophysical properties can be produced by alternative splicing of KCNMA1 precursor mRNA at several different sites."

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"Two distinct effects of PIP 2 underlie auxiliary subunit dependent modulation of Slo1 BK channels."

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"LRRC26 knockdown did not alter Ca (2+) sparks but reduced BK channel voltage sensitivity, which decreased channel apparent Ca (2+) sensitivity and transient BK current frequency and amplitude in myocytes."

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"In addition, disruption of the BK Ca gene KCNMA1 which encodes the alpha-subunit of the large conductance Ca 2+ -activated K + channel (BK Ca) led to both haplo-insufficiency and reduced BK Ca activity."

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"One caveat with this previous work is that the impact of BK channels on dendritic excitability has only been investigated using bath applications of BK channel blockers, which block both somatic and dendritic BK channels."

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"The results in our study provide insights into the different modulations of beta2 subunit between mammalian and Drosophila Slo1 and beta2 channels and structural basis underlie the activation and pre-inactivation of other BK (beta) complexes."

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"Mallotoxin (MTX), a selective activator of BK channel that lacks BKgamma1, dose-dependently activated BK currents in mASMCs, but not in mBSMCs."

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"In MCCs this is evident by comparing the BK channel types expressed in WT and Ca1.3 -/- MCCs using standard protocols of Ca 2+ pre-loading which maximally activate all available BK channels."

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"Interestingly, a recent functional study demonstrated that BK channel openers, such as Cym04 and NS1619, activate BK channels by functionally interacting with the C-linker, thereby mimicking site specific shortening of the C-linker."

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"In addition, iberiotoxin (100 nM), a widely used specific BK channel blocker which can block BK channels in various neurons, did not show a clear effect under control (n = 5) or ischemic (n = 4) conditions in SNr neurons (data not shown)."

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"A direct activator of KCNMA1, NS1619 (10 microM), significantly activated BK currents in MFK223 but not in MCF7 cells."

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"The BK channel gamma subunits (BKgamma) exhibit different tissue specific mRNA expression and may broadly modulate BK channels in different tissues XREF_BIBR."