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Inhibition of T-type voltage-gated calcium channels by a new scorpion toxin

Nature Neuroscience volume 1, pages 668–674 (1998)Cite this article

Abstract

The biophysical properties of T-type voltage-gated calcium channels are well suited to pacemaking and to supporting calcium flux near the resting membrane potential in both excitable and non-excitable cells. We have identified a new scorpion toxin (kurtoxin) that binds to the α 1G T-type calcium channel with high affinity and inhibits the channel by modifying voltage-dependent gating. This toxin distinguishes between α 1G T-type calcium channels and other types of voltage-gated calcium channels, including α 1A , α 1B , α 1C and α 1E . Like the other α-scorpion toxins to which it is related, kurtoxin also interacts with voltage-gated sodium channels and slows their inactivation. Kurtoxin will facilitate characterization of the subunit composition of T-type calcium channels and help determine their involvement in electrical and biochemical signaling.

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Figure 1: Purification of kurtoxin from scorpion venom.
Figure 2: Inhibition of α1G T-type calcium channels by kurtoxin.
Figure 3: Kurtoxin shifts the opening of the α1G T-type calcium channel to more depolarized voltages.
Figure 4: Kurtoxin slows activation and inactivation of α1G T-type calcium channels.
Figure 5: Concentration dependence of inhibition by kurtoxin.
Figure 6: Selectivity of kurtoxin for different voltage-gated calcium channels.
Figure 7: Kurtoxin slows inactivation of voltage-gated sodium channels.

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Acknowledgements

We thank Zhe Lu, Chinfei Chen and Yingying Li-Smerin for discussions.

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Authors and Affiliations

  1. Molecular Physiology and Biophysics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bldg. 36, Rm. 2C19, 36 Convent Drivex, MSC 4066, Bethesda, 20892, Maryland, USA

    Rosalind S-I. Chuang & Kenton J. Swartz

  2. Protein/Peptide Sequencing Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bldg. 36, Rm. 3B26, 36 Convent Drive, MSC 4066, Bethesda, 20892, Maryland, USA

    Howard Jaffe

  3. Department of Physiology, Loyola University Medical Center, 2160 South First Avenue, Maywood, 60153, Illinois, USA

    Leanne Cribbs & Edward Perez-Reyes

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  1. Rosalind S-I. Chuang
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Correspondence to Kenton J. Swartz.

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Chuang, RI., Jaffe, H., Cribbs, L. et al. Inhibition of T-type voltage-gated calcium channels by a new scorpion toxin. Nat Neurosci 1, 668–674 (1998). https://doi.org/10.1038/3669

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