title: Inhibition of martentoxin on neuronal BK channel subtype (alpha+beta4): implications for a novel interaction model.
abstract: Martentoxin as a 37-residue peptide was capable of blocking large-conductance Ca(2+)-activated K(+) (BK) channels in adrenal medulla chromaffin cells. This study investigated the pharmacological discrimination of martentoxin on BK channel subtypes. The results showed that the iberiotoxin-insensitive neuronal BK channels (alpha+beta4) could be potently blocked by martentoxin (IC(50) = approximately 80 nM). In contrast, the iberiotoxin-sensitive BK channel consisting of only alpha-subunit was less sensitive to martentoxin. Distinctively, martentoxin inhibited neuronal BK channels (alpha+beta4) with a novel interaction mode. Two possible interaction sites of neuronal BK channels (alpha+beta4) might be responsible for the binding with martentoxin: one for trapping and the other located at the pore region for blocking. In addition, the inhibition of martentoxin on neuronal BK channels (alpha+beta4) depended on cytoplasmic Ca(2+) concentration. On the other hand, in vivo experiments from EEG recordings suggested that neuronal BK channels (alpha+beta4) were the primary target of martentoxin. Therefore, this research not only sheds light on a unique ligand for neuronal BK channels (alpha+beta4), but also highlights a novel model approach for the interaction between K(+) channels and specific-ligands.
authors.affiliation: Graduate School of the Chinese Academy of Sciences, Institute of Physiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Shi
authors.forename: Hui Qiong
authors.initials: HQ
authors.lastname: He
authors.forename: Rong
authors.initials: R
authors.lastname: Zhao
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Duan
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Juan
authors.initials: J
authors.lastname: Yang
authors.forename: Jian Wei
authors.initials: JW
authors.lastname: Zhang
authors.forename: Xue Qin
authors.initials: XQ
authors.lastname: Shu
authors.forename: Ping
authors.initials: P
authors.lastname: Zheng
authors.forename: Yong Hua
authors.initials: YH
authors.lastname: Ji
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D004569:Electroencephalography / Q000187:drug effects; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D010455:Peptides / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012604:Scorpion Venoms / Q000633:toxicity*; D013379:Substrate Specificity
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D012604:Scorpion Venoms; C064719:iberiotoxin; D002118:Calcium