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J Pharmacol Exp Ther. 1996 Dec;279(3):1229-36.

Effects of omega-agatoxin-IVA and omega-conotoxin-MVIIC on perineurial Ca++ and Ca(++)-activated K+ currents of mouse motor nerve terminals.

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1
Department of Pharmacology, Michigan State University, East Lansing, USA.

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.

PMID:
8968345
[Indexed for MEDLINE]

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