ArticleThe Journal of biological chemistry2005
Structural determinants of L-type channel activation in segment IIS6 revealed by a retinal disorder.
Article in The Journal of biological chemistry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Identification of novel functional sites in the CaProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Inactivation of CaV1 and CaV2 channels.The Journal of general physiology · 2025Review
- Non-ionotropic voltage-gated calcium channel signaling.Channels (Austin, Tex.) · 2024Review
- Reverse-engineered models reveal differential membrane properties of autonomic and cutaneous unmyelinated fibers.PLoS computational biology · 2024Article
- Functional Characterization of Four Known Cav2.1 Variants Associated with Neurodevelopmental Disorders.Membranes · 2023Article
- The effect of alterations of schizophrenia-associated genes on gamma band oscillations.Schizophrenia (Heidelberg, Germany) · 2022Article
- Permeabilizing Cell Membranes with Electric Fields.Cancers · 2021Review
- Functional impact of a congenital stationary night blindness type 2 mutation depends on subunit composition of CaThe Journal of biological chemistry · 2020Article
- De novo CACNA1D CaPflugers Archiv : European journal of physiology · 2020Review
- Alterations in Schizophrenia-Associated Genes Can Lead to Increased Power in Delta Oscillations.Cerebral cortex (New York, N.Y. : 1991) · 2019Article
- Computational Modeling of Genetic Contributions to Excitability and Neural Coding in Layer V Pyramidal Cells: Applications to Schizophrenia Pathology.Frontiers in computational neuroscience · 2019Article
- β-Subunit of the voltage-gated CaProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Calcium channel gating.Pflugers Archiv : European journal of physiology · 2018Review
- Pleiotropic effects of schizophrenia-associated genetic variants in neuron firing and cardiac pacemaking revealed by computational modeling.Translational psychiatry · 2017Article
- Key role of segment IS4 in Cav1.2 inactivation: link between activation and inactivation.Pflugers Archiv : European journal of physiology · 2017Article
- Upward movement of IS4 and IIIS4 is a rate-limiting stage in CaPflugers Archiv : European journal of physiology · 2016Article
- An autism-associated mutation in CaV1.3 channels has opposing effects on voltage- and Ca(2+)-dependent regulation.Scientific reports · 2016Article
- Molecular Interactions in the Voltage Sensor Controlling Gating Properties of CaV Calcium Channels.Structure (London, England : 1993) · 2016Article
- State-dependent inter-repeat contacts of exceptionally conserved asparagines in the inner helices of sodium and calcium channels.Pflugers Archiv : European journal of physiology · 2015Article
- Methods for quantification of pore-voltage sensor interaction in Ca(V)1.2.Pflugers Archiv : European journal of physiology · 2014Article
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8 authors.
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Abstract
The mechanism of channel opening for voltage-gated calcium channels is poorly understood. The importance of a conserved isoleucine residue in the pore-lining segment IIS6 has recently been highlighted by functional analyses of a mutation (I745T) in the Ca(V)1.4 channel causing severe visual impairment (Hemara-Wahanui, A., Berjukow, S., Hope, C. I., Dearden, P. K., Wu, S. B., Wilson-Wheeler, J., Sharp, D. M., Lundon-Treweek, P., Clover, G. M., Hoda, J. C., Striessnig, J., Marksteiner, R., Hering, S., and Maw, M. A. (2005) Proc. Natl. Acad. Sci. U. S. A. 102, 7553-7558). In the present study we analyzed the influence of amino acids in segment IIS6 on gating of the Ca(V)1.2 channel. Substitution of Ile-781, the Ca(V)1.2 residue corresponding to Ile-745 in Ca(V)1.4, by residues of different hydrophobicity, size and polarity shifted channel activation in the hyperpolarizing direction (I781P > I781T > I781N > I781A > I781L). As I781P caused the most dramatic shift (-37 mV), substitution with this amino acid was used to probe the role of other residues in IIS6 in the process of channel activation. Mutations revealed a high correlation between the midpoint voltages of activation and inactivation. A unique kinetic phenotype was observed for residues 779-782 (LAIA) located in the lower third of segment IIS6; a shift in the voltage dependence of activation was accompanied by a deceleration of activation at hyperpolarized potentials, a deceleration of deactivation at all potentials (I781P and I781T), and decreased inactivation. These findings indicate that Ile-781 substitutions both destabilize the closed conformation and stabilize the open conformation of Ca(V)1.2. Moreover there may be a flexible center of helix bending at positions 779-782 of Ca(V)1.2. These four residues are completely conserved in high voltage-activated calcium channels suggesting that these channels may share a common mechanism of gating.
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