title: SO-3, a new O-superfamily conopeptide derived from Conus striatus, selectively inhibits N-type calcium currents in cultured hippocampal neurons.
abstract: Whole-cell currents in cultured hippocampal neurons were recorded to investigate the effects of SO-3, a new O-superfamily conopeptide derived from Conus striatus, on voltage-sensitive channels. SO-3 had no effect on voltage-sensitive sodium currents, delayed rectifier potassium currents, and transient outward potassium currents. Similar to the selective N-type calcium channel blocker omega-conotoxin MVIIA (MVIIA), SO-3 could concentration-dependently inhibit the high voltage-activated (HVA) calcium currents (I(Ca)). MVIIA(3 microM), 10 microM nimodipine, and 0.5 microM omega-agatoxin IVA (Aga) could selectively block the N-, L-, and P/Q-type I(Ca), which contributed approximately 32, approximately 38, and approximately 21% of the HVA currents in hippocampal neurons, respectively. About 31% of the total HVA currents were inhibited by 3 microM SO-3. SO-3 (3 microM) and 3 microM MVIIA inhibited the overlapping components of HVA currents, whereas no overlapping component was inhibited by 3 microM SO-3 and 10 microM nimodipine, or by 3 microM SO-3 and 0.5 microM Aga. Also, 3 microM SO-3 had no effect on R-type currents. SO-3 had less inhibitory effects on non-N-type HVA currents than MVIIA at higher concentrations (30 and 100 microM). The inhibitory effects of SO-3 and MVIIA on HVA currents were almost fully reversible. However, the recovery from block by MVIIA was more rapid than recovery from block by SO-3. It is concluded that SO-3 is a new omega-conotoxin selectively targeting N-type voltage-sensitive calcium channels. Considering the significance of N-type calcium channels for pain transduction, SO-3 may have therapeutic potential as a novel analgesic agent.
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Tai-Ping Road, Haidian District, Beijing 100850, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wen
authors.forename: Sheng
authors.initials: S
authors.lastname: Yang
authors.forename: Haifa
authors.initials: H
authors.lastname: Qiao
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Liu
authors.forename: Wenxia
authors.initials: W
authors.lastname: Zhou
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Peitang
authors.initials: P
authors.lastname: Huang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009553:Nimodipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020960:omega-Conotoxins / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D010455:Peptides; C482173:SO-3 conopeptide, Conus striatus; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; D009553:Nimodipine; C078452:ziconotide