title: Peptide toxins and small-molecule blockers of BK channels.
abstract: Large conductance, Ca(2+)-activated potassium (BK) channels play important roles in the regulation of neuronal excitability and the control of smooth muscle contractions. BK channels can be activated by changes in both the membrane potential and intracellular Ca(2+) concentrations. Here, we provide an overview of the structural and pharmacological properties of BK channel blockers. First, the properties of different venom peptide toxins from scorpions and snakes are described, with a focus on their characteristic structural motifs, including their disulfide bond formation pattern, the binding interface between the toxin and BK channel, and the functional consequence of the blockage of BK channels by these toxins. Then, some representative non-peptide blockers of BK channels are also described, including their molecular formula and pharmacological effects on BK channels. The detailed categorization and descriptions of these BK channel blockers will provide mechanistic insights into the blockade of BK channels. The structures of peptide toxins and non-peptide compounds could provide templates for the design of new channel blockers, and facilitate the optimization of lead compounds for further therapeutic applications in neurological disorders or cardiovascular diseases.
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei 230031, China.
authors.forename: Mu
authors.initials: M
authors.lastname: Yu
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei 230031, China.
authors.forename: San-ling
authors.initials: SL
authors.lastname: Liu
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Pei-bei
authors.initials: PB
authors.lastname: Sun
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Pan
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei 230031, China.|School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Chang-lin
authors.initials: CL
authors.lastname: Tian
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Long-hua
authors.initials: LH
authors.lastname: Zhang
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D015195:Drug Design; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors* / Q000502:physiology; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology; D012604:Scorpion Venoms / Q000494:pharmacology; D012910:Snake Venoms / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D007093:Imidazoles; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D026902:Potassium Channel Blockers; D011804:Quinolines; D012604:Scorpion Venoms; D012910:Snake Venoms