Skip to Main content Skip to Navigation
Journal articles

TRIP8b Splice Variants Form a Family of Auxiliary Subunits that Regulate Gating and Trafficking of HCN Channels in the Brain

Abstract : Hyperpolarization-activated cyclic nucleotide-regulated (HCN) channels, which generate the I(h) current, mediate a number of important brain functions. The HCN1 isoform regulates dendritic integration in cortical pyramidal neurons and provides an inhibitory constraint on both working memory in prefrontal cortex and spatial learning and memory in the hippocampus. Altered expression of HCN1 following seizures may contribute to the development of temporal lobe epilepsy. Yet the regulatory networks and pathways governing HCN channel expression and function in the brain are largely unknown. Here, we report the presence of nine alternative N-terminal splice forms of the brain-specific cytoplasmic protein TRIP8b and demonstrate the differential effects of six isoforms to downregulate or upregulate HCN1 surface expression. Furthermore, we find that all TRIP8b isoforms inhibit channel opening by shifting activation to more negative potentials. TRIP8b thus functions as an auxiliary subunit that provides a mechanism for the dynamic regulation of HCN1 channel expression and function.
Document type :
Journal articles
Complete list of metadatas

https://www.hal.inserm.fr/inserm-02768059
Contributor : Rebecca Ann Piskorowski <>
Submitted on : Thursday, June 4, 2020 - 10:21:31 AM
Last modification on : Thursday, June 4, 2020 - 3:12:33 PM

Links full text

Identifiers

Collections

Citation

Bina Santoro, Rebecca Piskorowski, Phillip Pian, Lei Hu, Haiying Liu, et al.. TRIP8b Splice Variants Form a Family of Auxiliary Subunits that Regulate Gating and Trafficking of HCN Channels in the Brain. Neuron, Elsevier, 2009, 62 (6), pp.802-813. ⟨10.1016/j.neuron.2009.05.009⟩. ⟨inserm-02768059⟩

Share

Metrics

Record views

18