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Updated: Mar 28, 2026
Single-Cell Calcium Imaging for Studying the Activation of Calcium Ion Channels
Published on: December 13, 2024
Modulating Ca²⁺ signals: a common theme for TMEM16, Ist2, and TMC
Karl Kunzelmann1, Ines Cabrita2, Podchanart Wanitchakool2
1Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany. Karl.Kunzelmann@vkl.uni-regensburg.de.
Abstract:
Since the discovery of TMEM16A (anoctamin 1, ANO1) as Ca(2+)-activated Cl(-) channel, the protein was found to serve different physiological functions, depending on the type of tissue. Subsequent reports on other members of the anoctamin family demonstrated a broad range of yet poorly understood properties. Compromised anoctamin function is causing a wide range of diseases, such as hearing loss (ANO2), bleeding disorder (ANO6), ataxia and dystonia (ANO3, 10), persistent borrelia and mycobacteria infection (ANO10), skeletal syndromes like gnathodiaphyseal dysplasia and limb girdle muscle dystrophy (ANO5), and cancer (ANO1, 6, 7). Animal models demonstrate CF-like airway disease, asthma, and intestinal hyposecretion (ANO1). Although present data indicate that ANO1 is a Ca(2+)-activated Cl(-) channel, it remains unclear whether all anoctamins form plasma membrane-localized or intracellular chloride channels. We find Ca(2+)-activated Cl(-) currents appearing by expression of most anoctamin paralogs, including the Nectria haematococca homologue nhTMEM16 and the yeast homologue Ist2. As recent studies show a role of anoctamins, Ist2, and the related transmembrane channel-like (TMC) proteins for intracellular Ca(2+) signaling, we will discuss the role of these proteins in generating compartmentalized Ca(2+) signals, which may give a hint as to the broad range of cellular functions of anoctamins.
Insights
Anoctamins, including TMEM16A, function as calcium-activated chloride channels. Their diverse roles in health and disease highlight the importance of understanding their cellular localization and signaling pathways.
Area of Science:
- Molecular Biology
- Cell Physiology
- Ion Channel Function
Background:
- TMEM16A (anoctamin 1) is a calcium-activated chloride channel with diverse physiological roles.
- Dysfunction of anoctamin family proteins is linked to various diseases, including hearing loss, bleeding disorders, neurological conditions, infections, skeletal syndromes, and cancer.
- While TMEM16A is known as a plasma membrane channel, the localization and function of other anoctamins remain poorly understood.
Purpose of the Study:
- To investigate the channel activity of anoctamin family members.
- To explore the potential for anoctamins to function as intracellular chloride channels.
- To discuss the role of anoctamins in intracellular calcium signaling and compartmentalization.
Main Methods:
- Expression of anoctamin paralogs in cellular systems.
- Electrophysiological recordings to detect calcium-activated chloride currents.
- Analysis of anoctamin function in yeast and fungal homologues.
Main Results:
- Most anoctamin paralogs, including fungal homologues, exhibit calcium-activated chloride currents upon expression.
- This suggests a conserved function across different species and potential roles beyond plasma membrane channels.
- Evidence points towards anoctamins, Ist2, and TMC proteins participating in intracellular calcium signaling.
Conclusions:
- Anoctamins likely function as calcium-activated chloride channels, with conserved properties across species.
- Their involvement in intracellular calcium signaling suggests a role in compartmentalized calcium dynamics.
- Further research into anoctamin localization and function is crucial for understanding their broad cellular roles and associated diseases.
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