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

The effects of the spider toxin omega-Aga-IIIA were studied on Ca channel currents in rat central neurons. In hippocampal CA1 pyramidal neurons, omega-Aga-IIIA blocked approximately 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 omega-Aga-IIIA abolished dihydropyridine-sensitive L-type current and blocked a substantial fraction of the omega-conotoxin (CgTX)-sensitive N-type and omega-Aga-IVA-sensitive P-type Ca currents. The high-threshold current remaining with saturating concentrations of nimodipine, CgTX, and omega-Aga-IVA was also partially blocked by omega-Aga-IIIA in a variety of central neurons. Block of P-type current by omega-Aga-IIIA was investigated in more detail in cerebellar Purkinje neurons. Block was potent (Kd approximately 0.5 nM), but incomplete and voltage dependent. Tail current activation curves showed that channel gating is shifted in the depolarizing direction by approximately 7 mV. The instantaneous current-voltage curve for P-type current was also altered; the toxin reduced Ba-carried inward currents by approximately 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.