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Updated: Feb 6, 2026

Pull-down of Calmodulin-binding Proteins
Published on: January 23, 2012
Lack of correlation between surface expression and currents in epileptogenic AB-calmodulin binding domain Kv7.2
Alessandro Alaimo1, Ainhoa Etxeberria1, Juan Camilo Gómez-Posada1
1a Instituto Biofisika , Consejo Superior de Investigaciones Científicas, CSIC, UPV/EHU , Leioa , Spain.
Abstract:
Heteromers of Kv7.2/Kv7.3 subunits constitute the main substrate of the neuronal M-current that limits neuronal hyper-excitability and firing frequency. Calmodulin (CaM) binding is essential for surface expression of Kv7 channels, and disruption of this interaction leads to diseases ranging from mild epilepsy to early onset encephalopathy. In this study, we addressed the impact of a charge neutralizing mutation located at the periphery of helix B (K526N). We found that, CaM binding and surface expression was impaired, although current amplitude was not altered. Currents were reduced at a faster rate after activation of a voltage-dependent phosphatase, suggesting that phosphatidylinositol-4,5-bisphosphate (PIP2) binding was weaker. In contrast, a charge neutralizing mutation located at the periphery of helix A (R333Q) did not affect CaM binding, but impaired trafficking and led to a reduction in current amplitude. Taken together, these results suggest that disruption of CaM-dependent or CaM-independent trafficking of Kv7.2/Kv7.3 channels can lead to pathology regardless of the consequences on the macroscopic ionic flow through the channel.
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