PT  - JOURNAL ARTICLE
AU  - McDonough, SI
AU  - Swartz, KJ
AU  - Mintz, IM
AU  - Boland, LM
AU  - Bean, BP
TI  - Inhibition of calcium channels in rat central and peripheral neurons by omega-conotoxin MVIIC
AID  - 10.1523/JNEUROSCI.16-08-02612.1996
DP  - 1996 Apr 15
TA  - The Journal of Neuroscience
PG  - 2612--2623
VI  - 16
IP  - 8
4099  - http://www.jneurosci.org/content/16/8/2612.short
4100  - http://www.jneurosci.org/content/16/8/2612.full
SO  - J. Neurosci.1996 Apr 15; 16
AB  - Inhibition of voltage-dependent calcium channels by omega-conotoxin MVIIC (omega-CTx-MVIIC) was studied in various types of rat neurons. When studied with 5 mM Ba2+ as charge carrier, omega-CTx-MVIIC block of N-type calcium channels in sympathetic neurons was potent, with half- block at 18 nM. Block of N-type channels had a rapid onset (tau approximately 1 sec at 1 microM omega-CTx-MVIIC) and quick reversibility (tau approximately 30 sec). The rate of block was proportional to toxin concentration, consistent with 1:1 binding of toxin to channels, with a rate constant (k on) of approximately 1 X 10(6) M-1. sec-1. Both potency and rate of block were reduced dramatically with increasing concentrations of extracellular Ba2+ omega- CTx-MVIIC also blocked P-type calcium channels in cerebellar Purkinje neurons, but both development and reversal of block were far slower than for N-type channels. The rate of block was proportional to toxin concentration, with k on -1.5 x 10(3) M-1. sec-1 at 5 mM Ba2+. From this value and an unblocking time constant of approximately 200 min, a dissociation constant of approximately 50 nM was estimated. Thus, block of P-type channels is potent but very slow. In hippocampal CA3 pyramidal neurons, omega-CTx-MVIIC blocked approximately 50% of the high-threshold calcium channel current; one component (approximately 20%) was blocked with the rapid kinetics expected for N-type channels, whereas the other component was blocked slowly. The component blocked slowly was reduced but not eliminated by preexposure to 200 nM or 1 microM omega-Aga-IVA.