PT - JOURNAL ARTICLE AU - Haoya Liang AU - Keith S. Elmslie TI - Rapid and Reversible Block of N-Type Calcium Channels (Ca<sub>V</sub> 2.2) by ω-Conotoxin GVIA in the Absence of Divalent Cations AID - 10.1523/JNEUROSCI.22-20-08884.2002 DP - 2002 Oct 15 TA - The Journal of Neuroscience PG - 8884--8890 VI - 22 IP - 20 4099 - http://www.jneurosci.org/content/22/20/8884.short 4100 - http://www.jneurosci.org/content/22/20/8884.full SO - J. Neurosci.2002 Oct 15; 22 AB - ω-Conotoxin GVIA (ωCGVIA) has been reported to be an irreversible blocker of N-type calcium channels (CaV 2.2). However, recent studies have demonstrated that the ωCGVIA off-rate is correlated with divalent cation concentration, because increasing [Ba2+]o accelerated the recovery from ωCGVIA block. This predicts that the dissociation of ωCGVIA from N-channels will be negligible in the absence of divalent cations. Surprisingly, we find that ωCGVIA block is rapidly reversible in divalent cation-free (0 Ba2+) external solutions in which current was carried by MA+. The recovery followed a single-exponential time course with τ = 31 sec. Isochronic measurements showed that, at 2 min after the removal of toxin, current returned to 86% of control in 0 Ba2+compared with 19% in 3 mm Ba2+. The off-rate of ωCGVIA from N-channels was dependent on [Ba2+]o, because, at an intermediate concentration (3 μmBa2+), N-current recovered with τ = 64 sec, significantly slower than that in 0 Ba2+ but faster than in 3 mm Ba2+. Recovery from ωCGVIA block was also observed when Cs+ or Na+ carried the current in divalent cation-free conditions. The off-rate was sensitive to [Ba2+]o only during washout, because current recovered slowly in the presence of 3 mmBa2+, even after it was blocked in 0 Ba2+. Assuming that the toxin is a pore blocker, our findings are consistent with a model in which Ba2+interacts at a site on the extracellular surface of the channel to regulate ωCGVIA dissociation from N-channels.