ArticleProceedings of the National Academy of Sciences of the United States of America2006
Switching off calcium-dependent inactivation in L-type calcium channels by an autoinhibitory domain.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 100 citations in OpenAlex.
- Calmodulinopathy variants impair CaV1.3 and CaV2.1 regulation.The Journal of general physiology · 2026Article
- Frequency responses of human magnetophosphene perception thresholds during dark adaptation point to rod modulation.Experimental physiology · 2026Article
- Exploring the potential for gene therapy in Cav1.4-related retinal channelopathies.Channels (Austin, Tex.) · 2025Review
- Role of the C-terminal domain in modifying pH-dependent regulation of CaChannels (Austin, Tex.) · 2025Article
- Calmodulin binding is required for calcium mediated TRPA1 desensitization.Nature communications · 2025Article
- Role of Dyadic Proteins in Proper Heart Function and Disease.International journal of molecular sciences · 2025Review
- Calcium channel-coupled transcription factors facilitate direct nuclear signaling.Research square · 2025Article
- L-Type Voltage-Gated CaBiochemistry · 2025Article
- Inactivation of CaV1 and CaV2 channels.The Journal of general physiology · 2025Review
- Role of the CaChannels (Austin, Tex.) · 2024Article
- A non-conducting role of the CaeLife · 2024Article
- A non-conducting role of the CabioRxiv : the preprint server for biology · 2024Article
- Effects of L-Type Voltage-Gated Calcium Channel (LTCC) Inhibition on Hippocampal Neuronal Death after Pilocarpine-Induced Seizure.Antioxidants (Basel, Switzerland) · 2024Article
- Calmodulin Mutations in Human Disease.Channels (Austin, Tex.) · 2023Review
- Regulation of Cardiac Cav1.2 Channels by Calmodulin.International journal of molecular sciences · 2023Review
- Regulation of Presynaptic Calcium Channels.Advances in neurobiology · 2023Article
- Calmodulin promotes a CaFEBS letters · 2022Article
- Calcium Channels in Retinal Function and Disease.Annual review of vision science · 2022Review
- Cav1.4 dysfunction and congenital stationary night blindness type 2.Pflugers Archiv : European journal of physiology · 2021Review
- Disturbed Presynaptic CaiScience · 2020Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The retinal L-type Ca2+ channel Cav1.4 is distinguished from all other members of the high voltage-activated (HVA) Ca2+ channel family by lacking Ca2+-calmodulin-dependent inactivation. In synaptic terminals of photoreceptors and bipolar cells, this feature is essential to translate graded membrane depolarizations into sustained Ca2+ influx and tonic glutamate release. The sequences conferring Ca2+-dependent inactivation (CDI) are conserved throughout the HVA calcium channel family, raising the question of how Cav1.4 manages to switch off CDI. Here, we identify an autoinhibitory domain in the distal C terminus of Cav1.4 that serves to abolish CDI. We show that this domain (ICDI, inhibitor of CDI) uncouples the molecular machinery conferring CDI from the inactivation gate by binding to the EF hand motif in the proximal C terminus. Deletion of ICDI completely restores Ca2+-calmodulin-mediated CDI in Cav1.4. CDI can be switched off again in the truncated Cav1.4 channel by coexpression of ICDI, indicating that ICDI works as an autonomous unit. Furthermore, we show that in the Cav1.2 l-type Ca2+-channel replacement of the distal C terminus by the corresponding sequence of Cav1.4 is sufficient to block CDI. This finding suggests that autoinhibition of CDI can be introduced principally into other Ca2+ channel types. Our data provide a previously undescribed perspective on the regulation of HVA calcium channels by Ca2+.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.