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Molecular characterization of a neuronal low-voltage-activated T-type calcium channel

Abstract

The molecular diversity of voltage-activated calcium channels was established by studies showing that channels could be distinguished by their voltage-dependence, deactivation and single-channel conductance1,2,3. Low-voltage-activated channels are called ‘T’ type because their currents are both transient (owing to fast inactivation) and tiny (owing to small conductance)2. T-type channels are thought to be involved in pacemaker activity, low-threshold calcium spikes, neuronal oscillations and resonance, and rebound burst firing4. Here we report the identification of a neuronal T-type channel. Our cloning strategy began with an analysis of Genbank sequences defined as sharing homology with calcium channels. We sequenced an expressed sequence tag (EST), then used it to clone a full-length complementary DNA from rat brain. Northern blot analysis indicated that this gene is expressed predominantly in brain, in particular the amygdala, cerebellum and thalamus. We mapped the human gene to chromosome 17q22, and the mouse gene to chromosome 11. Functional expression of the channel was measured in Xenopus oocytes. Based on the channel's distinctive voltage dependence, slow deactivation kinetics, and 7.5-pS single-channel conductance, we conclude that this channel is a low-voltage-activated T-type calcium channel.

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Figure 1: Alignment of the putative membrane spanning regions of α1G, α1C and α1E.
Figure 2: Distribution of α1G mRNA in rat and human.
Figure 3: Current–voltage (I–V) relationships of cloned α1G are compared to native T-type currents in NIE-115 cells and cloned α1E channels.
Figure 4: Deactivation and single-channel conductance of α1G currents.

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Acknowledgements

We thank J. Yang for expert technical support. We also thank the UK HGMP Resource Centre for the Genbridge 4 radiation hybrid mapping panel and the EUCIB mouse panel. This work was supported by grants from the NIH, Potts Foundation and the Medical Research Council. E.P.-R. is an established investigator of the American Heart Association.

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Correspondence to Edward Perez-Reyes.

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Perez-Reyes, E., Cribbs, L., Daud, A. et al. Molecular characterization of a neuronal low-voltage-activated T-type calcium channel. Nature 391, 896–900 (1998). https://doi.org/10.1038/36110

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