{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Liu X"],"funding":["National Natural Science Foundation of China"],"pagination":["e4506"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9703589"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["31(12)"],"pubmed_abstract":["Epilepsy is the results from the imbalance between inhibition and excitation in neural circuits, which is mainly treated by some chemical drugs with side effects. Gain-of-function of BK channels or knockout of its β4 subunit associates with spontaneous epilepsy. Currently, few reports were published about the efficacy of BK(α + β4) channel modulators in epilepsy prevention. Charybdotoxin is a non-specific inhibitor of BK and other K<sup>+</sup> channels. Here, by nuclear magnetic resonance (NMR) and other biochemical techniques, we found that charybdotoxin might interact with the extracellular loop of human β4 subunit (i.e., hβ4-loop) of BK(α + β4) channel at a molar ratio 4:1 (hβ4-loop vs. charybdotoxin). Charybdotoxin enhanced its ability to prevent K<sup>+</sup> current of BK(α + β4 H101Y) channel. The charybdotoxin Q18F variant selectively reduced the neuronal spiking frequency and increased interspike intervals of BK(α + β4) channel by π-π stacking interactions between its residue Phe<sup>18</sup> and residue His<sup>101</sup> of hβ4-loop. Moreover, intrahippocampal infusion of charybdotoxin Q18F variant significantly increased latency time of seizure, reduced seizure duration and seizure numbers on pentylenetetrazole-induced pre-sensitized rats, inhibited hippocampal hyperexcitability and c-Fos expression, and displayed neuroprotective effects on hippocampal neurons. These results implied that charybdotoxin Q18F variant could be potentially used for intractable epilepsy treatment by therapeutically targeting BK(α + β4) channel."],"journal":["Protein science : a publication of the Protein Society"],"pubmed_title":["Development of charybdotoxin Q18F variant as a selective peptide blocker of neuronal BK(α + β4) channel for the treatment of epileptic seizures."],"pmcid":["PMC9703589"],"funding_grant_id":["22177127","21977110","82074162","22174155"],"pubmed_authors":["Liu X","Li G","Tao J","Yao Y","Wang C","Cao C","Ji Y","Zhang S","Lan W","Xue H"],"additional_accession":[]},"is_claimable":false,"name":"Development of charybdotoxin Q18F variant as a selective peptide blocker of neuronal BK(α + β4) channel for the treatment of epileptic seizures.","description":"Epilepsy is the results from the imbalance between inhibition and excitation in neural circuits, which is mainly treated by some chemical drugs with side effects. Gain-of-function of BK channels or knockout of its β4 subunit associates with spontaneous epilepsy. Currently, few reports were published about the efficacy of BK(α + β4) channel modulators in epilepsy prevention. Charybdotoxin is a non-specific inhibitor of BK and other K<sup>+</sup> channels. Here, by nuclear magnetic resonance (NMR) and other biochemical techniques, we found that charybdotoxin might interact with the extracellular loop of human β4 subunit (i.e., hβ4-loop) of BK(α + β4) channel at a molar ratio 4:1 (hβ4-loop vs. charybdotoxin). Charybdotoxin enhanced its ability to prevent K<sup>+</sup> current of BK(α + β4 H101Y) channel. The charybdotoxin Q18F variant selectively reduced the neuronal spiking frequency and increased interspike intervals of BK(α + β4) channel by π-π stacking interactions between its residue Phe<sup>18</sup> and residue His<sup>101</sup> of hβ4-loop. Moreover, intrahippocampal infusion of charybdotoxin Q18F variant significantly increased latency time of seizure, reduced seizure duration and seizure numbers on pentylenetetrazole-induced pre-sensitized rats, inhibited hippocampal hyperexcitability and c-Fos expression, and displayed neuroprotective effects on hippocampal neurons. These results implied that charybdotoxin Q18F variant could be potentially used for intractable epilepsy treatment by therapeutically targeting BK(α + β4) channel.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2026-06-21T03:16:51.674Z","creation":"2025-04-04T09:39:31.64Z"},"accession":"S-EPMC9703589","cross_references":{"pubmed":["36369672"],"doi":["10.1002/pro.4506"]}}