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

Edward Perez-Reyes (), Leanne L. Cribbs, Asif Daud, Antonio E. Lacerda, Jane Barclay, Magali P. Williamson, Margaret Fox, Michele Rees and Jung-Ha Lee
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Edward Perez-Reyes: Loyola University Medical Center
Leanne L. Cribbs: Loyola University Medical Center
Asif Daud: Loyola University Medical Center
Antonio E. Lacerda: Rammelkamp Center for Research & Education, MetroHealth Medical Center
Jane Barclay: The Rayne Institute, University College London Medical School
Magali P. Williamson: The Rayne Institute, University College London Medical School
Margaret Fox: MRC Human Biochemical Genetics Unit, The Galton Laboratory
Michele Rees: The Rayne Institute, University College London Medical School
Jung-Ha Lee: Loyola University Medical Center

Nature, 1998, vol. 391, issue 6670, 896-900

Abstract: 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.

Date: 1998
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DOI: 10.1038/36110

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