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Journal of Neuroscience, Vol 14, 5011-5027, Copyright © 1994 by Society for Neuroscience
omega-Conotoxin block of N-type calcium channels in frog and rat sympathetic neurons
LM Boland, JA Morrill and BP Bean
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115.
Block of N-type Ca channels by omega-conotoxin GVIA (CgTx) was studied in
freshly dissociated bullfrog and rat sympathetic neurons. With 2-5 mM Ba as
charge carrier, CgTx blocked almost all of the high-threshold Ca channel
current recorded in the presence of nimodipine (3 microM) to block L-type
Ca channels. Toxin block reversed slowly (time constant approximately 1 hr)
in frog cells and even more slowly in rat cells. CgTx block was faster and
more potent in rat cells than frog cells. The rate of block was
proportional to CgTx concentration, consistent with 1:1 binding of CgTx to
channels. When the external Ba concentration was increased, the development
of block was slower, consistent with competition between CgTx and Ba for a
binding site. The recovery from block was somewhat faster in higher
external Ba. Some cells had significant current remaining in saturating
concentrations of nimodipine and CgTx, especially with high Ba
concentrations in the external solution. The current resistant to
nimodipine and CgTx was activated at lower depolarizations than the
CgTx-sensitive current and had faster activation and inactivation kinetics,
but unlike low- threshold T-type current, the resistant current had rapidly
decaying tail currents.
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