ArticleProceedings of the National Academy of Sciences of the United States of America2012
Calcium homeostasis modulator 1 (CALHM1) is the pore-forming subunit of an ion channel that mediates extracellular Ca2+ regulation of neuronal excitability.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
96 citing papers in PubMed.
- Transient infrared laser exposure modulates calcium activity in cortical dendritic spines.Biophotonics discovery · 2026Article
- Article
- CALHM5 deficiency alleviates aortic aneurysm by regulating smooth muscle calcium homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Calhm6 Governs Macrophage Polarization Through Chp1-Camk4-Creb1 Axis and Ectosomal Delivery in Inflammatory Responses.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Structure-based virtual screening for selective connexin hemichannel blockers: a historical perspective on the discovery of a small organic inhibitor.Frontiers in pharmacology · 2026Article
- The CALHM1 blocker CGP37157 increases seizure severity during status epilepticus in adult mice.Purinergic signalling · 2025Article
- Identification and classification of ion-channels across the tree of life provide functional insights into understudied CALHM channels.bioRxiv : the preprint server for biology · 2025Article
- Biology, function and structure of the calcium homeostasis modulator family.The Journal of physiology · 2025Review
- Intracellular calcium imaging for agonist screening.Biophysics reports · 2025Article
- A mechanism of CALHM1 ion channel gating.American journal of physiology. Cell physiology · 2025Article
- Intracellular cAMP signaling-induced CaPflugers Archiv : European journal of physiology · 2025Article
- Model-based evaluation of connexin hemichannel permeability.Computational and structural biotechnology journal · 2025Article
- Article
- Control of astrocytic CaBiological research · 2024Article
- Metabolic memory: mechanisms and diseases.Signal transduction and targeted therapy · 2024Review
- High calcium concentrations reduce cellular excitability of mouse MNTB neurons.Brain research · 2023Article
- Negative modulation of mitochondrial calcium uniporter complex protects neurons against ferroptosis.Cell death & disease · 2023Article
- Neurovirulent cytokines increase neuronal excitability in a model of coronavirus-induced neuroinflammation.Intensive care medicine experimental · 2023Article
- Cytosolic calcium: Judge, jury and executioner of neurodegeneration in Alzheimer's disease and beyond.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Review
- Review
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
Extracellular Ca(2+) (Ca(2+)(o)) plays important roles in physiology. Changes of Ca(2+)(o) concentration ([Ca(2+)](o)) have been observed to modulate neuronal excitability in various physiological and pathophysiological settings, but the mechanisms by which neurons detect [Ca(2+)](o) are not fully understood. Calcium homeostasis modulator 1 (CALHM1) expression was shown to induce cation currents in cells and elevate cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) in response to removal of Ca(2+)(o) and its subsequent addback. However, it is unknown whether CALHM1 is a pore-forming ion channel or modulates endogenous ion channels. Here we identify CALHM1 as the pore-forming subunit of a plasma membrane Ca(2+)-permeable ion channel with distinct ion permeability properties and unique coupled allosteric gating regulation by voltage and [Ca(2+)](o). Furthermore, we show that CALHM1 is expressed in mouse cortical neurons that respond to reducing [Ca(2+)](o) with enhanced conductance and action potential firing and strongly elevated [Ca(2+)](i) upon Ca(2+)(o) removal and its addback. In contrast, these responses are strongly muted in neurons from mice with CALHM1 genetically deleted. These results demonstrate that CALHM1 is an evolutionarily conserved ion channel family that detects membrane voltage and extracellular Ca(2+) levels and plays a role in cortical neuronal excitability and Ca(2+) homeostasis, particularly in response to lowering [Ca(2+)](o) and its restoration to normal levels.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.