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Ion Channels in Immune Cells
Published in Shyam S. Bansal, Immune Cells, Inflammation, and Cardiovascular Diseases, 2022
Devasena Ponnalagu, Shridhar Sanghvi, Shyam S. Bansal, Harpreet Singh
Connexins are ubiquitous, integral membrane proteins present in almost all of the cells of the body. Connexins are known to form cell-cell communication in tissues and between the extracellular environment and cytoplasm by forming gap junctions. In electrically excitable cells like cardiomyocytes, connexins serve as a powerful coordinator for allowing the cell-to-cell passage of ions to facilitate uniform electrical conduction throughout the heart159–161.
Keratitis–Ichthyosis–Deafness Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
With a short half-life of 2–4 h, connexins participate in intracellular connexin−protein interaction, cell−extracellular space exchange, and cell−cell communication through formation of hemichannels and GJC Specifically, six connexin subunits gather together as hemichannel (or gap junction hemichannel, also known as connexon) in the endoplasmic reticulum or Golgi body and then move to cellular membranes, where two hemichannels join through hydrophobic interactions to form GJC, which is an aqueous pore between the cytoplasm of two adjacent cells, facilitating the exchange of ions (K+, Ca2+), signaling molecules (IP3, cAMP, cGMP, ATP) and metabolites (e.g., glucose, sugar, amino acid, glutathione) (Figure 42.1). Via these activities, connexins activate signaling pathways and affect cellular phenotypes. Not surprisingly, total or partial connexin dysfunctions may lead to a variety of genetic disorders such as skin abnormalities, cardiopathies, neurodegenerative and developmental diseases, cataracts, hereditary deafness, and cancer (collectively known as connexinopathies) (Table 42.1) [4–6].
Role of Cell-to-Cell Coupling in Control of Myometrial Contractility and Labor
Published in Robert E. Garfield, Thomas N. Tabb, Control of Uterine Contractility, 2019
Gap junctions consist of pores that connect the interiors of two cells (Figure 6). The pore allows passage of neutral and charged molecules to move between cells. The pores are composed of proteins, termed connexins,4 which span the plasma membranes to form a channel. The gap junction proteins have been cloned and antibodies have been prepared to the connexins. In the myometrium a 43-Kdalton protein, termed connexin 43, is thought to be the major component of the gap junction. Connexin 43 is also found in other tissues, including cardiac cells, where it is thought to be required for synchronizing cardiac contractility.4 Connexin 43 is a protein composed of 382 amino acids with two serine residues that may be phosphorylated (Figure 7). Each gap junction can be made up from a few to thousands of channels and each channel is constructed from a group of six connexin proteins, a hemichannel, in one cell aligned symmetrically with six connexins in the adjacent connected cell. The two hemichannels each have a gate, so that each cell can functionally regulate conductance. In some cases the state of phosphorylation has been correlated with changes in functional states of gap junctional communication.80 Phosphorylation of some types of connexins is thought to lead to the open configuration in some cells, whereas the dephosphorylated form of the same connexin is associated with the open state in other cells.
The complex interplay between diabetes mellitus and atrial fibrillation
Published in Expert Review of Cardiovascular Therapy, 2022
Mehmet Yildiz, Carl J. Lavie, Daniel P. Morin, Ahmet Afsin Oktay
Experimental studies have explored possible pathophysiological mechanisms underlying the link between DM and AF. A comprehensive discussion of these pathophysiological mechanisms is beyond the scope of our review. These mechanisms were reviewed in detail in other publications and might be broadly summarized in four categories as follows: 1) atrial structural remodeling through atrial dilation and increased myocardial fibrosis due to increased growth factors; 2) atrial proarrhythmic remodeling secondary to activation of AGE/RAGE signaling (advanced glycation end-products and receptor for advanced glycation end-products), oxidative stress, inflammation, and increased production of reactive oxygen species due to mitochondrial dysfunction; 3) atrial electrical remodeling through altered connexin expression and calcium regulation, and 4) atrial autonomic dysfunction through increased sympathetic activity and decreased parasympathetic activity [45–49].
The cardiac toxicity of radiotherapy – a review of characteristics, mechanisms, diagnosis, and prevention
Published in International Journal of Radiation Biology, 2021
In the meantime, other molecular mechanisms such as DNA damage, mitochondrial dysfunction, and microRNA changes have been raised by some researchers. DNA breakage due to radiation directly has been recognized as the initiation of cell apoptosis. Meanwhile, ROS can regulate DNA methylation, histone methylation, and acetylation. And the release of ROS can induce genomic instability (Yakovlev 2013; Yahyapour et al. 2018). Mitochondrial dysfunction and irreversible damage are vital in cell apoptosis after radiation. Excessive ROS leads to endoplasmic reticulum (ER) damage and promotes the release of calcium. ROS and calcium overload are involved in MPT which depolarizes the mitochondrial membrane and decouples oxidative phosphorylation (Sridharan et al. 2014). And mitochondria can produce more ROS as a vicious cycle (Wang et al. 2019). Gene regulators such as microRNA are involved in cardiac hypertrophy by irradiation (Kura et al. 2017). Thus microRNA has potential as a bio-marker and radioprotective agent of cardiovascular injury or inflammation in RIHD (Kenchegowda et al. 2018; Kura et al. 2019). From what has been discussed above, greater efforts are needed to identify the clinical applications of connexin proteins and their channels.
Left Ventricular Reverse Remodeling in Heart Failure: Remission to Recovery
Published in Structural Heart, 2021
Jacinthe Boulet, Mandeep R. Mehra
The association between malignant ventricular arrhythmias and cardiac remodeling has been established through various well-defined mechanisms. Remodeling is associated with prolongation of the action potential, changes in sodium, potassium, and calcium channels, including alterations in the sodium/calcium exchanger.50,51 It also disturbs the gap junctional intercellular communication as evidenced by modification of the normal distribution and labeling intensity of connexin 43, the most prominent gap junction protein expressed in the normal heart.50,51 These alterations may be associated with prolongation of the QT interval and promote early after depolarizations and increase the risk of malignant arrhythmias.50 Remodeling also causes the accumulation of myocardial fibrillar collagen involving the epimysium, perimysium, and endomysium, three connective tissue compartments surrounding muscle bundles (epicardium and endocardium), muscle fibers, and single muscles, respectively. The development of fibrosis through increased collagen content may lead to electrical conduction disorders and arrhythmogenesis, especially reentrant arrhythmias facilitated by activation delays with electrogram fractionation through fibrotic muscles.50,52 Altogether, those changes associated with cardiac remodeling increase the risk of sustained ventricular tachycardia and ventricular fibrillation, thus raising patients’ risk of sudden cardiac death.8,53