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Journal of Neuroscience, Vol 14, 2844-2853, Copyright © 1994 by Society for Neuroscience
Block of Ca channels in rat central neurons by the spider toxin omega- Aga-IIIA
IM Mintz
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115.
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.
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