Molecular and Functional Properties of the Human α1G Subunit That Forms T-type Calcium Channels*

By A. Monteil, J. Chemin, E. Bourinet, G. Mennessier, P. Lory, J. Nargeot. Journal of Biological Chemistry, 2000

223 citations recorded by the source corpus.

We describe here several novel properties of the human α1G subunit that forms T-type calcium channels. The partial intron/exon structure of the corresponding geneCACNA1G was defined and several α1G isoforms were identified, especially two isoforms that exhibit a distinct III-IV loop: α1G-a and α1G-b. Northern blot and dot blot analyses indicated that α1G mRNA is predominantly expressed in the brain, especially in thalamus, cerebellum, and substantia nigra. Additional experiments have also provided evidence that α1G mRNA is expressed at a higher level during fetal life in nonneuronal tissues (i.e.kidney, heart, and lung). Functional expression in HEK 293 cells of a full-length cDNA encoding the shortest α1G isoform identified to date, α1G-b, resulted in transient, low threshold activated Ca2+ currents with the expected permeability ratio (I Sr >I Ca ≥ I Ba) and channel conductance (∼7 pS). These properties, together with slowly deactivating tail currents, are typical of those of native T-type Ca2+ channels. This α1G-related current was inhibited by mibefradil (IC50 = 2 μm) and weakly blocked by Ni2+ ions (IC50 = 148 μm) and amiloride (IC50 > 1 mm). We showed that steady state activation and inactivation properties of this current can generate a “window current” in the range of −65 to −55 mV. Using neuronal action potential waveforms, we show that α1G channels produce a massive and sustained Ca2+ influx due to their slow deactivation properties. These latter properties would account for the specificity of Ca2+ influx via T-type channels that occurs in the range of physiological resting membrane potentials, differing considerably from the behavior of other Ca2+ channels.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/004e6e00ee9a24561742878ebb0766a3a548b514

How researchers see this paper

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In Cellular and Molecular Neuroscience

1. E. Perez-Reyes
2. J. Chemin
3. J. Nargeot
4. P. Lory
5. R. Kass
6. J. Nerbonne

In Molecular Biology

1. E. Perez-Reyes
2. J. Chemin
3. J. Nargeot
4. P. Lory
5. J. Nerbonne
6. R. Kass

Citations in the corpus

• Neuronal T-type α1H Calcium Channels Induce Neuritogenesis and Expression of High-Voltage-Activated Calcium Channels in the NG108–15 Cell Line (2002, background): “3)] (Cribbs et al., 1998; Perez-Reyes et al., 1998; Klugbauer et al., 1999; Lee et al. 1999a; Williams et al., 1999; Monteil et al., 2000a,b; McRory et al., 2001) has enabled the molecular investigation of T-channel functions.”
• Molecular physiology of low-voltage-activated t-type calcium channels. (2003, background): “3 are predominantly expressed in brain (228, 288, 289, 324).”
• Specific contribution of human T‐type calcium channel isotypes (α1G, α1H and α1I) to neuronal excitability (2002, methodology): “…Purkinje neuron activities The pacemaker activity occurring in Purkinje neurons of the cerebellum is generated by intrinsic properties of these neurons, which abundantly express T-channels (Gruol & Franklin, 1997; Raman & Bean, 1999a; Talley et al. 1999; Monteil et al. 2000a; Raman et al. 2000).”
• Alternatively Spliced α1G (CaV3.1) Intracellular Loops Promote Specific T-Type Ca2+ Channel Gating Properties (2001, unknown): “It is therefore important to note that splicing of the 1G subunit within the III-IV linker affects a PKA/PKC consensus site that is present in the a isoforms but removed in the b isoforms (Monteil et al., 2000a).”