IndraLab

Statements

FMR1 activates KCNMA1. 11 / 11
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"FMRP Modulates BK Channel Calcium Sensitivity."
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"To examine the specific mechanisms by which FMRP modulates BK channel function, we isolated BK currents (as a paxilline or iberiotoxin sensitive component) using AP clamp."
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"Genetic upregulation of BK channels has been shown to correct many deficits in the mouse model of FXS, suggesting that FMRP directly modulates BK channel activity [169,170]."
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"Fmr1 and BKbeta4 double knockout mice were generated to genetically upregulate BK channel activity in the absence of FMRP."
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"Loss of FMRP reduces BK channel activity and causes excessive AP broadening (XREF_FIG), leading to elevated presynaptic Ca 2+ influx and increased glutamate release during repetitive activity in both hippocampal and cortical pyramidal neurons."
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"Single-channel analyses revealed that FMRP loss reduced BK channel open probability, and this defect was compensated in dKO mice."
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"For example, it has been demonstrated in hippocampal CA3 pyramidal neurons that FMRP modulates BK channel activity by sequestering its regulatory β4 subunit (30)."
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"Loss of FMRP causes reduced BK channel activity and excessive AP broadening, leading in turn to elevated presynaptic calcium influx, increased synaptic transmission and STP during repetitive activity."
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"In Fragile X syndrome (FXS), a disorder characterized by intellectual disability and autism-like behaviors, the fragile X mental retardation protein (FMRP) in the central nervous system directly modulates BK channel function to regulate action potential duration [16, 23]."
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"Indeed, studies of both Fmr1 KO mice and stem cell-derived neurons from FXS patients report that the loss of FMRP reduces BK channel activity, which in turn leads to a wide range of functional consequences."
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"We used the Horrigan-Aldrich ( HA ) allosteric model ( Horrigan and Aldrich , 2002 ) to obtain information about the molecular mechanisms of BK channel modulation by FMRP ."
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