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The Journal of Neuroscience, October 1, 2000, 20(19):7174-7182
Low-Affinity Blockade of Neuronal N-Type Ca Channels by the
Spider Toxin  -Agatoxin-IVA
Serguei S.
Sidach and
Isabelle M.
Mintz
Department of Pharmacology and Experimental Therapeutics, Boston
University Medical Center, Boston, Massachusetts 02118
The recognition of neuronal Ca channel diversity has led to
considerable efforts to identify useful classification criteria. Here,
we revisit the pharmacological definition of P- and Q-type Ca channels,
which is based on their respective high and low sensitivity to the
spider  -agatoxin-IVA (-Aga-IVA), using whole-cell recordings of
the Ca channel currents carried by 5 mM
Ba2+ in isolated rat subthalamic and sympathetic
neurons. In subthalamic neurons, -Aga-IVA (1 µM)
targeted multiple Ca channels. One population was blocked with high
potency. These channels carried 50.4 ± 3.4% (n = 5) of the control current and showed the same
inactivation kinetics and voltage-dependent high affinity for
-Aga-IVA as do prototypic P-type Ca channels. Other Ca channels were
targeted with weaker potency. This heterogeneous population contributed to 14.0 ± 1.7% (n = 5) of the control
current. It included N-type Ca channels as well as high-threshold Ca
channels that displayed the pharmacological signature of Q-type Ca
channels but resembled P-type Ca channels in their gating properties.
N-type Ca current block by -Aga-IVA (1 µM) was further
investigated in sympathetic neurons, which mainly express this Ca
channel type. Block was incomplete (~30% of the control current).
Its relief at positive potentials was consistent with -Aga-IVA
acting as a channel-gating modifier. These effects did not reflect a
complete loss of selectivity, because -Aga-IVA (1 µM)
had no effect on subthalamic Na and K currents or their T- and L-type
Ca currents. Our data confirm that -Aga-IVA is a selective P-type Ca
channel blocker. However, its diminished selectivity in the micromolar
range limits its usefulness for functional studies of Q-type Ca channels.
Key words:
spider toxin; -agatoxin; subthalamic neuron; sympathetic neuron; Purkinje neuron; N-type Ca channel; Q-type Ca
channel; P-type Ca channel
Copyright © 2000 Society for Neuroscience 0270-6474/00/20197174-09$05.00/0
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