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Updated: Mar 29, 2026

Single-Cell Calcium Imaging for Studying the Activation of Calcium Ion Channels
Published on: December 13, 2024
Calcium homeostasis modulator (CALHM) ion channels
Zhongming Ma1, Jessica E Tanis2, Akiyuki Taruno3
1Department of Physiology, Perelman School of Medicine, University of Pennsylvania, 720 Clinical Research Bldg., 415 Curie Blvd., Philadelphia, PA, 19104, USA. zma@mail.med.upenn.edu.
Calcium homeostasis modulator 1 (CALHM1) is a voltage- and Ca(2+)-gated ion channel. It plays key roles in brain neuron excitability and taste perception by mediating ATP release.
Area of Science:
- Ion channel physiology
- Molecular biology
- Neuroscience
Background:
- Calcium homeostasis modulator 1 (CALHM1) is a recently identified plasma membrane ion channel.
- CALHM1 and its homolog CLHM-1 are regulated by membrane voltage and extracellular Ca(2+) concentration.
- CALHM channels share structural similarities with connexins and pannexins.
Purpose of the Study:
- To elucidate the gating mechanisms and physiological roles of CALHM1.
- To characterize the structure and ion permeability of CALHM channels.
- To investigate the function of CALHM1 in neuronal excitability and taste signaling.
Main Methods:
- Electrophysiological recordings to study channel gating.
- Structural analysis based on homology to related gene families.
- Analysis of CALHM1 expression and function in mammalian and C. elegans models.
Main Results:
- CALHM1 and CLHM-1 gating is allosterically regulated by both membrane voltage and extracellular Ca(2+).
- CALHM channels form hexamers with a pore diameter of ~14 Å, permeable to both cations and anions, including Ca(2+) and ATP.
- CALHM1 is crucial for cortical neuron excitability and ATP release in taste bud cells, while CLHM-1 affects locomotion in C. elegans.
Conclusions:
- CALHM1 is a versatile ion channel with significant physiological roles in the nervous system and sensory perception.
- The dual regulation by voltage and Ca(2+) allows CALHM channels to respond to changing physiological conditions.
- CALHM channels represent a novel target for understanding and potentially treating neurological and sensory disorders.
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