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We investigated targeting mechanisms of Na and K channels to the intercalated disk (ICD) of cardiomyocytes. Patch clamp and surface biotinylation data show reciprocal downregulation of each other's surface density. Mutagenesis of the Kir6.2 ankyrin binding site disrupts this functional coupling. Duplex patch clamping and Angle SICM recordings show that I and I functionally co-localize at the rat ICD, but not at the lateral membrane. Quantitative STORM imaging show that Na and K channels are localized close to each other and to AnkG, but not to AnkB, at the ICD. Peptides corresponding to Nav1.5 and Kir6.2 ankyrin binding sites dysregulate targeting of both Na and K channels to the ICD, but not to lateral membranes. Finally, a clinically relevant gene variant that disrupts K channel trafficking also regulates Na channel surface expression. The functional coupling between these two channels need to be considered when assessing clinical variants and therapeutics.
This article was published in the following journal.
Arrhythmogenic cardiomyopathy (ACM) is an inherited arrhythmia syndrome characterized by severe structural and electrical cardiac phenotypes, including myocardial fibrofatty replacement and sudden car...
To elaborate the mechanism of miR-150 in the regulation of the NF-κB signal pathway in intervertebral disc degeneration (IDD) by targeting P2X7.
TRPV2 is a well-conserved channel protein expressed in almost all tissues. Cardiomyocyte TRPV2 is expressed in the intercalated discs of the cardiac sarcomeres where it is involved in maintaining the ...
Adult mammals are unable to regenerate their hearts after cardiac injury; largely due to the incapacity of cardiomyocytes to undergo cell division. However, mammalian embryonic and foetal cardiomyocyt...
The dynamic disc model refers to the ability of a spinal disc's position to be manipulated by body postures and movements. Research on lumbar discs has indicated movement of the anterior and posterior...
The aim of this study is to investigate the efficacy and safety of intercalated combination of erlotinib and radiotherapy for patients with EGFR-mutant, unresectable, locally advanced NSCL...
This will be the first prospective study where patients will be selected on the basis of two measures of the EGFR pathway. The study will assess prospectively the efficacy of erlotinib as ...
This study will look at the result of using the FLD device as an artificial lumbar disc. The study will compare the safety and effectiveness of the FLD artificial lumbar disc to an already...
Epidermal growth factor receptor (EGFR) mutations occur in up to 50% of Asian patients with non-small cell lung cancer (NSCLC). Treatment of advanced NSCLC patients with EGFR-tyrosine kina...
The aim of this study is described as follows, 1. To establish a validated method to test cough reflex sensitivity conducted by transient receptor potential vanilloid 1(TRPV1). ...
A subgroup of TRP cation channels named after melastatin protein. They have the TRP domain but lack ANKYRIN repeats. Enzyme domains in the C-terminus leads to them being called chanzymes.
A subgroup of TRP cation channels that contain 3-4 ANKYRIN repeats and a conserved C-terminal domain. Members are highly expressed in the CENTRAL NERVOUS SYSTEM. Selectivity for calcium over sodium ranges from 0.5 to 10.
A subgroup of TRP cation channels named after vanilloid receptor. They are very sensitive to TEMPERATURE and hot spicy food and CAPSAICIN. They have the TRP domain and ANKYRIN repeats. Selectivity for CALCIUM over SODIUM ranges from 3 to 100 fold.
The dissolving of the NUCLEUS PULPOSUS, the semi-gelatinous tissue of a displaced INTERVERTEBRAL DISC. It is usually achieved by the direct injection of a proteolytic enzyme, especially CHYMOPAPAIN, into the herniated disc.
Endogenously produced lipid-soluble gaseous molecules which function as neurotransmitters and signal mediators targeting ION CHANNELS and transporters.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...