Persistent PKA activation redistributes NaV1.5 to the cell surface of adult rat ventricular myocytes

被引:2
作者
Bernas, Tytus [1 ]
Seo, John [2 ]
Wilson, Zachary T. [2 ]
Tan, Bi-hua [3 ]
Deschenes, Isabelle [3 ]
Carter, Christiane [4 ]
Liu, Jinze [4 ]
Tseng, Gea-Ny [2 ]
机构
[1] Virginia Commonwealth Univ, Dept Anat & Neurobiol, Richmond, VA USA
[2] Virginia Commonwealth Univ, Dept Physiol & Biophys, Richmond, VA 23284 USA
[3] Ohio State Univ, Dept Physiol & Cell Biol, Columbus, OH USA
[4] Virginia Commonwealth Univ, Massey Ctr Bioinformat Shared Resource, Richmond, VA USA
基金
美国国家卫生研究院;
关键词
CARDIAC SODIUM-CHANNEL; REGULATES MICROTUBULE DYNAMICS; TRAFFICKING; PHOSPHORYLATION; EXPRESSION; PROTEINS; CLUSTERS; COMPLEX;
D O I
10.1085/jgp.202313436
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
During chronic stress, persistent activation of cAMP-dependent protein kinase (PKA) occurs, which can contribute to protective or maladaptive changes in the heart. We sought to understand the effect of persistent PKA activation on Na(V)1.5 channel distribution and function in cardiomyocytes using adult rat ventricular myocytes as the main model. PKA activation with 8CPT-cAMP and okadaic acid (phosphatase inhibitor) caused an increase in Na+ current amplitude without altering the total Na(V)1.5 protein level, suggesting a redistribution of Na(V)1.5 to the myocytes' surface. Biotinylation experiments in HEK293 cells showed that inhibiting protein trafficking from intracellular compartments to the plasma membrane prevented the PKA-induced increase in cell surface Na(V)1.5. Additionally, PKA activation induced a time-dependent increase in microtubule plus-end binding protein 1 (EB1) and clustering of EB1 at myocytes' peripheral surface and intercalated discs (ICDs). This was accompanied by a decrease in stable interfibrillar microtubules but an increase in dynamic microtubules along the myocyte surface. Imaging and coimmunoprecipitation experiments revealed that Na(V)1.5 interacted with EB1 and beta-tubulin, and both interactions were enhanced by PKA activation. We propose that persistent PKA activation promotes Na(V)1.5 trafficking to the peripheral surface of myocytes and ICDs by providing dynamic microtubule tracks and enhanced guidance by EB1. Our proposal is consistent with an increase in the correlative distribution of Na(V)1.5, EB1, and beta-tubulin at these subcellular domains in PKA-activated myocytes. Our study suggests that persistent PKA activation, at least during the initial phase, can protect impulse propagation in a chronically stressed heart by increasing Na(V)1.5 at ICDs.
引用
收藏
页数:25
相关论文
共 47 条
[11]   New Insights in Cardiac β-Adrenergic Signaling During Heart Failure and Aging [J].
de Lucia, Claudio ;
Eguchi, Akito ;
Koch, Walter J. .
FRONTIERS IN PHARMACOLOGY, 2018, 9
[12]   MECHANISMS AND PHYSIOLOGICAL IMPLICATIONS OF COOPERATIVE GATING OF CLUSTERED ION CHANNELS [J].
Dixon, Rose E. ;
Navedo, Manuel F. ;
Binder, Marc D. ;
Santana, L. Fernando .
PHYSIOLOGICAL REVIEWS, 2022, 102 (03) :1159-1210
[13]   Oxidative stress decreases microtubule growth and stability in ventricular myocytes [J].
Drum, Benjamin M. L. ;
Yuan, Can ;
Li, Lei ;
Liu, Qinghang ;
Wordeman, Linda ;
Santana, L. Fernando .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2016, 93 :32-43
[14]   A practical guide to evaluating colocalization in biological microscopy [J].
Dunn, Kenneth W. ;
Kamocka, Malgorzata M. ;
McDonald, John H. .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2011, 300 (04) :C723-C742
[15]   Association with SERCA2a directs phospholamban trafficking to sarcoplasmic reticulum from a nuclear envelope pool [J].
He, Wenbo ;
Huang, Dayang ;
Guo, Shuai ;
Wang, Danning ;
Guo, Jin ;
Cala, Steven E. ;
Chen, Zhenhui .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2020, 143 :107-119
[16]   Dynamic and Irregular Distribution of RyR2 Clusters in the Periphery of Live Ventricular Myocytes [J].
Hiess, Florian ;
Detampel, Pascal ;
Nolla-Colomer, Carme ;
Vallmitjana, Alex ;
Ganguly, Anutosh ;
Amrein, Matthias ;
ter Keurs, Henk E. D. J. ;
Benitez, Raul ;
Hove-Madsen, Leif ;
Chen, S. R. Wayne .
BIOPHYSICAL JOURNAL, 2018, 114 (02) :343-354
[17]   Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells [J].
Iourgenko, V ;
Zhang, WJ ;
Mickanin, C ;
Daly, I ;
Jiang, C ;
Hexham, JM ;
Orth, AP ;
Miraglia, L ;
Meltzer, J ;
Garza, D ;
Chirn, GW ;
McWhinnie, E ;
Cohen, D ;
Skelton, J ;
Terry, R ;
Yu, Y ;
Bodian, D ;
Buxton, FP ;
Zhu, JA ;
Song, CZ ;
Labow, MA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (21) :12147-12152
[18]   S-Palmitoylation of junctophilin-2 is critical for its role in tethering the sarcoplasmic reticulum to the plasma membrane [J].
Jiang, Min ;
Hu, Junping ;
White, Frances K. H. ;
Williamson, Judy ;
Klymchenko, Andrey S. ;
Murthy, Akshay ;
Workman, Samuel W. ;
Tseng, Gea-Ny .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2019, 294 (36) :13487-13501
[19]   Adult Ventricular Myocytes Segregate KCNQ1 and KCNE1 to Keep the IKs Amplitude in Check Until When Larger IKs Is Needed [J].
Jiang, Min ;
Wang, Yuhong ;
Tseng, Gea-Ny .
CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY, 2017, 10 (06)
[20]   Detyrosinated microtubules modulate mechanotransduction in heart and skeletal muscle [J].
Kerr, Jaclyn P. ;
Robison, Patrick ;
Shi, Guoli ;
Bogush, Alexey I. ;
Kempema, Aaron M. ;
Hexum, Joseph K. ;
Becerra, Natalia ;
Harki, Daniel A. ;
Martin, Stuart S. ;
Raiteri, Roberto ;
Prosser, Benjamin L. ;
Ward, Christopher W. .
NATURE COMMUNICATIONS, 2015, 6