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Updated: May 9, 2026
In Vivo Calcium Imaging in C. elegans Body Wall Muscles
Published on: October 20, 2019
CLHM-1 is a functionally conserved and conditionally toxic Ca2+-permeable ion channel in Caenorhabditis elegans
Jessica E Tanis1, Zhongming Ma, Predrag Krajacic
1Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Abstract:
Disruption of neuronal Ca(2+) homeostasis contributes to neurodegenerative diseases through mechanisms that are not fully understood. A polymorphism in CALHM1, a recently described ion channel that regulates intracellular Ca(2+) levels, is a possible risk factor for late-onset Alzheimer's disease. Since there are six potentially redundant CALHM family members in humans, the physiological and pathophysiological consequences of CALHM1 function in vivo remain unclear. The nematode Caenorhabditis elegans expresses a single CALHM1 homolog, CLHM-1. Here we find that CLHM-1 is expressed at the plasma membrane of sensory neurons and muscles. Like human CALHM1, C. elegans CLHM-1 is a Ca(2+)-permeable ion channel regulated by voltage and extracellular Ca(2+). Loss of clhm-1 in the body-wall muscles disrupts locomotory kinematics and biomechanics, demonstrating that CLHM-1 has a physiologically significant role in vivo. The motility defects observed in clhm-1 mutant animals can be rescued by muscle-specific expression of either C. elegans CLHM-1 or human CALHM1, suggesting that the function of these proteins is conserved in vivo. Overexpression of either C. elegans CLHM-1 or human CALHM1 in neurons is toxic, causing degeneration through a necrotic-like mechanism that is partially Ca(2+) dependent. Our data show that CLHM-1 is a functionally conserved ion channel that plays an important but potentially toxic role in excitable cell function.
Insights
The CALHM1 ion channel
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Neuronal calcium (Ca2+) homeostasis disruption is linked to neurodegenerative diseases.
- A CALHM1 gene polymorphism is a risk factor for Alzheimer's disease, but its in vivo function is unclear.
- CALHM1 is a calcium-permeable ion channel regulating intracellular Ca2+ levels.
Purpose of the Study:
- To investigate the in vivo function and conservation of the CALHM1 ion channel using its C. elegans homolog, CLHM-1.
- To determine the physiological and pathophysiological roles of CLHM-1 in excitable cells.
Main Methods:
- Utilized the nematode Caenorhabditis elegans as a model organism.
- Examined CLHM-1 expression in sensory neurons and muscles.
- Assessed the effects of clhm-1 gene deletion and overexpression on motility and neuronal function.
- Performed rescue experiments using C. elegans CLHM-1 and human CALHM1.
Main Results:
- CLHM-1 is expressed in C. elegans muscles and neurons and functions as a Ca2+-permeable ion channel.
- Loss of clhm-1 in muscles impairs locomotion, indicating a significant physiological role.
- Muscle-specific expression of C. elegans CLHM-1 or human CALHM1 rescues motility defects, showing functional conservation.
- Overexpression of CLHM-1 or CALHM1 in neurons leads to degeneration via a Ca2+-dependent necrotic-like mechanism.
Conclusions:
- CLHM-1 is a functionally conserved ion channel with essential roles in muscle function.
- CALHM1/CLHM-1 plays a critical, yet potentially toxic, role in the function of excitable cells.
- Understanding CALHM1 function is crucial for neurodegenerative disease research, particularly Alzheimer's disease.
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