Block of Ca channels in rat central neurons by the spider toxin ω-Aga-IIIA

Abstract

The effects of the spider toxin ω-Aga-IIIA were studied on Ca channel currents in rat central neurons. In hippocampal CA1 pyramidal neurons, ω-Aga-IIIA blocked ∼70% of the high-threshold Ca currents and had no effect on low-threshold T-type current. Occlusion experiments with blockers of L-, N-, and P-type Ca currents showed that ω-Aga-IIIA abolished dihydropyridine-sensitive L-type current and blocked a substantial fraction of the ω-conotoxin (CgTX)-sensitive N-type and ω-Aga-IVA-sensitive P-type Ca currents. The highthreshold current remaining with saturating concentrations of nimodipine, CgTX, and ω-Aga-IVA was also partially blocked by ω-Aga-IIIA in a variety of central neurons. Block of P-type current by ω-Aga-IIIA was investigated in more detail in cerebellar Purkinje neurons. Block was potent (Kd ∼ 0.5 nM), but incomplete and voltage dependent. Tail current activation curves showed that channel gating is shifted in the depolarizing direction by ∼7 mV. The instantaneous current-voltage curve for P-type current was also altered; the toxin reduced Ba-carried inward currents by ∼40% and had little effect on Cs-carried outward currents. The partial, voltage-dependent reduction of P-type Ca current can be accounted for by a combination of toxin effects on channel permeation and gating.