title: Triton X-100 inhibits L-type voltage-operated calcium channels.
abstract: Triton X-100 (TX-100) is a nonionic detergent frequently used at millimolar concentrations to disrupt cell membranes and solubilize proteins. At low micromolar concentrations, TX-100 has been reported to inhibit the function of potassium channels. Here, we have used electrophysiological and functional techniques to examine the effects of TX-100 on another class of ion channels, L-type voltage-operated calcium channels (VOCCs). TX-100 (30 nmol·L(-1) to 3 μmol·L(-1)) caused reversible concentration-dependent inhibition of recombinant L-type VOCC (CaV 1.2) currents and of native L-type VOCC currents recorded from rat vascular smooth muscle cells and cardiac myocytes, and murine and human pancreatic β-cells. In functional studies, TX-100 (165 nmol·L(-1) to 3.4 μmol·L(-1)) caused concentration-dependent relaxation of rat isolated mesenteric resistance arteries prestimulated with phenylephrine or KCl. This effect was independent of the endothelium. TX-100 (1.6 μmol·L(-1)) inhibited depolarization-induced exocytosis in both murine and human isolated pancreatic β-cells. These data indicate that at concentrations within the nanomolar to low micromolar range, TX-100 significantly inhibits L-type VOCC activity in a number of cell types, an effect paralleled by inhibition of cell functions dependent upon activation of these channels. This inhibition occurs at concentrations below those used to solubilize proteins and may compromise the use of solutions containing TX-100 in bioassays.
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.
authors.forename: Deepak
authors.initials: D
authors.lastname: Narang
authors.forename: Paul M
authors.initials: PM
authors.lastname: Kerr
authors.forename: Jason
authors.initials: J
authors.lastname: Baserman
authors.forename: Raymond
authors.initials: R
authors.lastname: Tam
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Gavin
authors.initials: G
authors.lastname: Searle
authors.forename: Jocelyn E
authors.initials: JE
authors.lastname: Manning-Fox
authors.forename: Isabelle M
authors.initials: IM
authors.lastname: Paulsen
authors.forename: Janna L
authors.initials: JL
authors.lastname: Kozuska
authors.forename: Patrick E
authors.initials: PE
authors.lastname: MacDonald
authors.forename: Peter E
authors.initials: PE
authors.lastname: Light
authors.forename: Andrew
authors.initials: A
authors.lastname: Holt
authors.forename: Frances
authors.initials: F
authors.lastname: Plane
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002460:Cell Line; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D017830:Octoxynol / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects
chemical_list: D020746:Calcium Channels, L-Type; D010656:Phenylephrine; D011189:Potassium Chloride; D017830:Octoxynol; D002118:Calcium