title: Enhancement effects of martentoxin on glioma BK channel and BK channel (α+β1) subtypes.
abstract: BACKGROUND
  BK channels are usually activated by membrane depolarization and cytoplasmic Ca(2+). Especially,the activity of BK channel (α+β4) can be modulated by martentoxin, a 37 residues peptide, with Ca(2+)-dependent manner. gBK channel (glioma BK channel) and BK channel (α+β1) possessed higher Ca(2+) sensitivity than other known BK channel subtypes.
  
  
  RESULTS
  The present study investigated the modulatory characteristics of martentoxin on these two BK channel subtypes by electrophysiological recordings, cell proliferation and Ca(2+) imaging. In the presence of cytoplasmic Ca(2+), martentoxin could enhance the activities of both gBK and BK channel (α+β1) subtypes in dose-dependent manner with EC(50) of 46.7 nM and 495 nM respectively, while not shift the steady-state activation of these channels. The enhancement ratio of martentoxin on gBK and BK channel (α+β1) was unrelated to the quantitative change of cytoplasmic Ca(2+) concentrations though the interaction between martentoxin and BK channel (α+β1) was accelerated under higher cytoplasmic Ca(2+). The selective BK pore blocker iberiotoxin could fully abolish the enhancement of these two BK subtypes induced by martentoxin, suggesting that the auxiliary β subunit might contribute to the docking for martentoxin. However, in the absence of cytoplasmic Ca(2+), the activity of gBK channel would be surprisingly inhibited by martentoxin while BK channel (α+β1) couldn't be affected by the toxin.
  
  
  CONCLUSIONS
  Thus, the results shown here provide the novel evidence that martentoxin could increase the two Ca(2+)-hypersensitive BK channel subtypes activities in a new manner and indicate that β subunit of these BK channels plays a vital role in this enhancement by martentoxin.
authors: Lab of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai, People's Republic of China.
authors: Jie
authors: J
authors: Tao
authors: Jian
authors: J
authors: Shi
authors: Li
authors: L
authors: Yan
authors: Ying
authors: Y
authors: Chen
authors: Yan Hong
authors: YH
authors: Duan
authors: Pin
authors: P
authors: Ye
authors: Qi
authors: Q
authors: Feng
authors: Jian Wei
authors: JW
authors: Zhang
authors: Xue Qin
authors: XQ
authors: Shu
authors: Yong Hua
authors: YH
authors: Ji
mesh_terms: D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D012604:Scorpion Venoms / Q000494:pharmacology*
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D012604:Scorpion Venoms; C471035:martentoxin, Buthus martensi