Dysfunction in Ankyrin-B Disrupts Heart Rate Regulation by Altering the Membrane Abundance of GIRK Channels
Abstract
Ankyrin-B (AnkB), encoded by ANK2, is essential for ion channel localization in the heart. We investigated its role in regulating sinoatrial node (SAN) responses to autonomic input. AnkB-haploinsufficient (AnkB+/-) mice showed baseline bradycardia, heightened SAN response to β-adrenergic stimulation, and increased heart rate variability. These mice exhibited reduced ICa,L and SAN sarcoplasmic reticulum Ca2+ content, unchanged IK,ACh density, but impaired IK,ACh desensitization. AnkB interacts with GIRK1/4 subunits, and its loss in cardiomyocyte-specific knockout mice reduced GIRK1 membrane localization. Our findings support that AnkB deficiency disrupts autonomic regulation of SAN function through downregulation of ICa,L and the reduction in IK,ACh desensitization.
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BibTeX
@article{li2026dysfunction,
title = {{Dysfunction in Ankyrin-B Disrupts Heart Rate Regulation by Altering the Membrane Abundance of GIRK Channels}},
author = {Jingdong Li and Crystal F Kline and Omer Cavus and John T Bobik and Nipun Malhotra and Jagun Raghavan and Sarah S Takenaka and Junie Kwak and Ryan J Cordeiro and Eleanor J Mohler and Emma Dudley and Xianyao Xu and Drew M Nassal and Yuejin Wu and Thomas J Hund and Matteo E Mangoni and Peter J Mohler and Mona El Refaey},
journal = {JACC : Basic to Translational Science},
year = {2026},
month = nov,
doi = {10.1016/j.jacbts.2026.101647},
url = {https://hal.science/hal-05850209v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Dysfunction in Ankyrin-B Disrupts Heart Rate Regulation by Altering the Membrane Abundance of GIRK Channels
AU - Jingdong Li
AU - Crystal F Kline
AU - Omer Cavus
AU - John T Bobik
AU - Nipun Malhotra
AU - Jagun Raghavan
AU - Sarah S Takenaka
AU - Junie Kwak
AU - Ryan J Cordeiro
AU - Eleanor J Mohler
AU - Emma Dudley
AU - Xianyao Xu
AU - Drew M Nassal
AU - Yuejin Wu
AU - Thomas J Hund
AU - Matteo E Mangoni
AU - Peter J Mohler
AU - Mona El Refaey
PY - 2026
DA - 2026/11/03
JO - JACC : Basic to Translational Science
DO - 10.1016/j.jacbts.2026.101647
UR - https://hal.science/hal-05850209v1
AB - Ankyrin-B (AnkB), encoded by ANK2, is essential for ion channel localization in the heart. We investigated its role in regulating sinoatrial node (SAN) responses to autonomic input. AnkB-haploinsufficient (AnkB+/-) mice showed baseline bradycardia, heightened SAN response to β-adrenergic stimulation, and increased heart rate variability. These mice exhibited reduced ICa,L and SAN sarcoplasmic reticulum Ca2+ content, unchanged IK,ACh density, but impaired IK,ACh desensitization. AnkB interacts with GIRK1/4 subunits, and its loss in cardiomyocyte-specific knockout mice reduced GIRK1 membrane localization. Our findings support that AnkB deficiency disrupts autonomic regulation of SAN function through downregulation of ICa,L and the reduction in IK,ACh desensitization.
SN - 2452-302X
ER -