title: The activation effect of hainantoxin-I, a peptide toxin from the Chinese spider, Ornithoctonus hainana, on intermediate-conductance Ca2+-activated K+ channels.
abstract: Intermediate-conductance Ca2+-activated K+ (IK) channels are calcium/calmodulin-regulated voltage-independent K+ channels. Activation of IK currents is important in vessel and respiratory tissues, rendering the channels potential drug targets. A variety of small organic molecules have been synthesized and found to be potent activators of IK channels. However, the poor selectivity of these molecules limits their therapeutic value. Venom-derived peptides usually block their targets with high specificity. Therefore, we searched for novel peptide activators of IK channels by testing a series of toxins from spiders. Using electrophysiological experiments, we identified hainantoxin-I (HNTX-I) as an IK-channel activator. HNTX-I has little effect on voltage-gated Na+ and Ca2+ channels from rat dorsal root ganglion neurons and on the heterologous expression of voltage-gated rapidly activating delayed rectifier K+ channels (human ether-à-go-go-related gene; human ERG) in HEK293T cells. Only 35.2% ± 0.4% of the currents were activated in SK channels, and there was no effect on BK channels. We demonstrated that HNTX-I was not a phrenic nerve conduction blocker or acutely toxic. This is believed to be the first report of a peptide activator effect on IK channels. Our study suggests that the activity and selectivity of HNTX-I on IK channels make HNTX-I a promising template for designing new drugs for cardiovascular diseases.
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China. huangpengfei7@163.com.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Huang
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China. yiya-180@163.com.
authors.forename: Yiya
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China. eva8023chen@sina.com.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China. zlzhuli@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China. dazhongyin002@126.com.
authors.forename: Dazhong
authors.initials: D
authors.lastname: Yin
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China. xiongzhizeng@gmail.com.
authors.forename: Xiongzhi
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China. liangsp@hunnu.edu.cn.
authors.forename: Songping
authors.initials: S
authors.lastname: Liang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003058:Cockroaches; D005260:Female; D005727:Ganglia, Spinal; D057809:HEK293 Cells; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010455:Peptides / Q000494:pharmacology* / Q000633:toxicity; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D017207:Rats, Sprague-Dawley; D013111:Spider Venoms / Q000494:pharmacology* / Q000633:toxicity; D013112:Spiders; D023382:Toxicity Tests, Acute; D014118:Toxins, Biological / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D013111:Spider Venoms; D014118:Toxins, Biological