title: Effects of omega-agatoxin-IVA and omega-conotoxin-MVIIC on perineurial Ca++ and Ca(++)-activated K+ currents of mouse motor nerve terminals.
abstract: Effects of omega-agatoxin-IVA (omega-Aga-IVA) and omega-conotoxin-MVIIC (omega-CTx-MVIIC) on mouse motor nerve terminal Ca+2 currents and Ca(+2)-activated K+ currents (IK,Ca) were compared using the triangularis sterni preparation and perineurial recording techniques. omega-Aga-IVA caused concentration- and time-dependent block of both the fast (ICa-f) and slow (ICa-s) components of Ca+2 current. Low concentrations (10 nM) caused preferential block of ICa-s. Higher concentrations (100-150 nM) of omega-Aga-IVA blocked ICa-f effectively. omega-CTx-MVIIC blocked both ICa-s and ICa-f with equal sensitivity; however, higher concentrations and longer exposure times than those required for omega-Aga-IVA were needed. omega-CTx-MVIIC could block the residual ICa-f that remained after pretreatment with Cd+2 or omega-Aga-IVA. Increasing the extracellular Ca+2 concentration partially antagonized the effects of both omega-Aga-IVA and omega-CTx-MVIIC on ICa-s and ICa-f. Washing the preparation with toxin-free solution only slightly antagonized the effect of omega-Aga-IVA and was ineffective in omega-CTx-MVIIC-treated preparations. Low concentrations of omega-Aga-IVA and omega-CTx-MVIIC increased the duration of IK,Ca whereas higher concentrations reduced the amplitude of IK,Ca. Thus, at mouse motor nerve terminals, both omega-Aga-IVA- and omega-CTx-MVIIC-sensitive Ca+2 currents exist. omega-Aga-IVA appears to be more selective in blocking nerve terminal Ca+2 current than does omega-CTx-MVIIC. Paradoxically, block of ICa-s alone by omega-Aga-IVA and, to a lesser extent, omega-CTx-MVIIC was associated with increased duration of IK,Ca whereas block of ICa-s and ICa-f by omega-Aga-IVA and omega-CTx-MVIIC was associated with reduced amplitude of IK,Ca.
authors.affiliation: Department of Pharmacology, Michigan State University, East Lansing, USA.
authors.forename: Y F
authors.initials: YF
authors.lastname: Xu
authors.forename: W D
authors.initials: WD
authors.lastname: Atchison
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D051379:Mice; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010455:Peptides / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D013111:Spider Venoms / Q000494:pharmacology*; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins
chemical_list: D010455:Peptides; D015221:Potassium Channels; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D002118:Calcium