TY - JOUR T1 - Characterization of presynaptic calcium channels with omega-conotoxin MVIIC and omega-grammotoxin SIA: role for a resistant calcium channel type in neurosecretion. JF - Molecular Pharmacology JO - Mol Pharmacol SP - 348 LP - 353 VL - 47 IS - 2 AU - T J Turner AU - R A Lampe AU - K Dunlap Y1 - 1995/02/01 UR - http://molpharm.aspetjournals.org/content/47/2/348.abstract N2 - The peptide Ca2+ channel antagonists omega-conotoxin (omega-CTX) MVIIC and omega-grammotoxin (omega-GTX) SIA were studied by measuring their effects on the release of [3H]glutamate from rat brain synaptosomes. The pseudo-first-order association constant for omega-CTX MVIIC (1.1 x 10(4) M-1 sec-1) was small, relative to that for omega-GTX SIA (3.6 x 10(5) M-1 sec-1). Equilibrium experiments showed that omega-CTX MVIIC blocked approximately 70% of Ca(2+)-dependent glutamate release evoked by 30 mM KCl (IC50 approximately 200 nM), whereas omega-GTX SIA virtually eliminated release, with lower potency (IC50 approximately 700 nM). At stronger depolarizations (60 mM KCl), neither toxin (at 1 microM) showed significant block of release, but when these or other Ca2+ channel antagonists (omega-CTX GVIA or omega-agatoxin IVA) were used in combination a substantial fraction of release was blocked. [3H]Glutamate release that was resistant to omega-CTX MVIIC was characterized with respect to its sensitivity to block by omega-GTX SIA and the inorganic blocker Ni2+. Both omega-GTX SIA and Ni2+ were relatively weak blockers of the resistant release. These results suggest that a previously uncharacterized Ca2+ channel exists in nerve terminals and can be distinguished on the basis of its resistance to omega-CTX MVIIC and its weak sensitivity to omega-GTX SIA and Ni2+. Thus, at least three channel types (P, N, and a "resistant" type) contribute to excitation-secretion coupling in nerve terminals. ER -