![]() ![]() Structure of the voltage-gated calcium channel Ca v1.1 at 3.6 Å resolution. Structure of the voltage-gated calcium channel Ca v1.1 complex. Ziconotide: indications, adverse effects, and limitations in managing refractory chronic pain. Effectiveness and safety of intrathecal ziconotide: interim analysis of the patient registry of intrathecal ziconotide management (PRIZM). Preferential interaction of ω-conotoxins with inactivated N-type Ca 2+ channels. Structural determinants of the blockade of N-type calcium channels by a peptide neurotoxin. ![]() Omega-conotoxin: direct and persistent blockade of specific types of calcium channels in neurons but not muscle. Targeting N-type and T-type calcium channels for the treatment of pain. Targeting chronic and neuropathic pain: the N-type calcium channel comes of age. ![]() Suppression of inflammatory and neuropathic pain symptoms in mice lacking the N-type Ca 2+ channel. Voltage-gated calcium channels and their auxiliary subunits: physiology and pathophysiology and pharmacology. Alternative splicing in the voltage-sensing region of N-type CaV2.2 channels modulates channel kinetics. Ziconotide for treatment of severe chronic pain. Schmidtko, A., Lötsch, J., Freynhagen, R. Ziconotide: neuronal calcium channel blocker for treating severe chronic pain. Pharmacotherapeutic potential of omega-conotoxin MVIIA (SNX-111), an N-type neuronal calcium channel blocker found in the venom of Conus magus. The physiology, pathology, and pharmacology of voltage-gated calcium channels and their future therapeutic potential. Selective role of N-type calcium channels in neuronal migration. Molecular cloning of the α-1 subunit of an ω-conotoxin-sensitive calcium channel. Our studies reveal the molecular basis for Ca v2.2-specific pore blocking by ziconotide and establish the framework for investigating electromechanical coupling in Ca v channels.ĭubel, S. Three of the voltage-sensing domains (VSDs) are in a depolarized state, whereas the VSD of repeat II exhibits a down conformation that is stabilized by Ca v2-unique intracellular segments and a phosphatidylinositol 4,5-bisphosphate molecule. To accommodate ziconotide, the ECL of repeat III and α2δ-1 have to tilt upward concertedly. Ziconotide is thoroughly coordinated by helices P1 and P2, which support the selectivity filter, and the extracellular loops (ECLs) in repeats II, III and IV of α1. Here we present cryo-electron microscopy structures of human Ca v2.2 (comprising the core α1 and the ancillary α2δ-1 and β3 subunits) in the presence or absence of ziconotide. Ziconotide is a Ca v2.2-specific peptide pore blocker that has been clinically used for treating intractable pain 4, 5, 6. The neuronal-type (N-type) voltage-gated calcium (Ca v) channels, which are designated Ca v2.2, have an important role in the release of neurotransmitters 1, 2, 3. ![]()
0 Comments
Leave a Reply. |
Details
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |