title: Opening of ligand-gated cation channel families by calpain inhibitors.
abstract: The class of Ca2+-permeable cation channels is composed of large families with six transmembrane segments including transient receptor potential, vanilloid receptor (VR), polycystin, epithelial calcium channels and melastatin (MLS). However, most of them are functionally silent and unexpressed in mammalian cells. An investigation of associated proteins made us believe that the blockade of calpain opens the silent channels. Using 1 microM of blockers in whole cellular patch pipette fill we measured currents of Chinese hamster ovary cells transfected by VR-like 1 and 2, polycystin-2, or a MLS-like new member (MLS3S). Significant conductance of every clone with a characteristic rectification by blockers was demonstrated. The permeability of Ca2+ to them is similar to that reported. Western blot suggested that blockers did not affect the assembly of the protein but enabled its cleavage. Therefore, investigation of these families with the blockers may boost our knowledge of electrophysiologic function.
authors.affiliation: Department of Pharmacology, Jichi Medical School 3311-1, Yakushiji, Minamikawachi, 329-0498, Tochigi, Japan
authors.forename: Makoto
authors.initials: M
authors.lastname: Suzuki
authors.forename: Gaku
authors.initials: G
authors.lastname: Ohki
authors.forename: Toshio
authors.initials: T
authors.lastname: Mochizuki
authors.forename: Stefan
authors.initials: S
authors.lastname: Somlo
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ishibashi
authors.forename: Masashi
authors.initials: M
authors.lastname: Imai
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D002154:Calpain / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000502:physiology; D003001:Cloning, Molecular; D006224:Cricetinae; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004594:Electrophysiology; D015640:Ion Channel Gating / Q000502:physiology; D007976:Leupeptins / Q000494:pharmacology*; D008024:Ligands; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D011955:Receptors, Drug / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D050396:TRPP Cation Channels; D014162:Transfection
chemical_list: D002118:Calcium; D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D002154:Calpain; D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D008024:Ligands; D008565:Membrane Proteins; D011955:Receptors, Drug; D050396:TRPP Cation Channels; C033668:calpastatin; C032854:leupeptin