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Hypoxic Regulation of the Large-Conductance, Calcium and Voltage-Activated Potassium Channel, BK
Hypoxia is a condition characterized by a reduction of cellular oxygen levels derived from alterations in oxygen balance. Hypoxic events trigger changes in cell-signaling cascades, oxidative stress, activation of pro-inflammatory molecules, and growth factors, influencing the activity of various ion channel families and leading to diverse cardiovascular diseases such as myocardial infarction, ischemic stroke, and hypertension. The large-conductance, calcium and voltage-activated potassium channel (BK) has a central role in the mechanism of oxygen (O2) sensing and its activity has been related to the hypoxic response. BK ch...
Source: Frontiers in Physiology - December 22, 2021 Category: Physiology Source Type: research

Kidney Ischemia/Reperfusion Injury Induces Changes in the Drug Transporter Expression at the Blood –Brain Barrier in vivo and in vitro
Ischemia/reperfusion injury is a major cause of acute kidney injury (AKI). AKI is characterized by a sudden decrease in kidney function, systemic inflammation, oxidative stress, and dysregulation of the sodium, potassium, and water channels. While AKI leads to uremic encephalopathy, epidemiological studies have shown that AKI is associated with a subsequent risk for developing stroke and dementia. To get more insights into kidney–brain crosstalk, we have created an in vitro co-culture model based on human kidney cells of the proximal tubule (HK-2) and brain microvascular endothelial cells (BMEC). The HK-2 cell line was g...
Source: Frontiers in Physiology - November 12, 2020 Category: Physiology Source Type: research

Sodium Fluctuations in Astroglia and Their Potential Impact on Astrocyte Function
Astrocytes are the main cell type responsible for the regulation of brain homeostasis, including the maintenance of ion gradients and neurotransmitter clearance. These processes are tightly coupled to changes in the intracellular sodium (Na+) concentration. While activation of the sodium-potassium-ATPase (NKA) in response to an elevation of extracellular K+ may decrease intracellular Na+, the cotransport of transmitters, such as glutamate, together with Na+ results in an increase in astrocytic Na+. This increase in intracellular Na+ can modulate, for instance, metabolic downstream pathways. Thereby, astrocytes are capable ...
Source: Frontiers in Physiology - August 11, 2020 Category: Physiology Source Type: research

Relationship Between Electrical Instability and Pumping Performance During Ventricular Tachyarrhythmia: Computational Study
There are representative electrical parameters for understanding the mechanism of reentrant waves in studies on tachyarrhythmia, namely the action potential duration (APD), dominant frequency, phase singularity, and filament. However, there are no studies that have directly identified the correlation between these electrophysiological parameters and cardiac contractility. Therefore, we have identified individual and integrative correlations between these electrical phenomena and contractility during tachyarrhythmia by deriving regression equations and also investigated the electrophysiological parameters affecting cardiac ...
Source: Frontiers in Physiology - March 23, 2020 Category: Physiology Source Type: research

Impaired Activity of Ryanodine Receptors Contributes to Calcium Mishandling in Cardiomyocytes of Metabolic Syndrome Rats
Conclusion Principal findings of this work are that abnormal Ca2+ transient amplitude, contractile dysfunction; and impaired relaxation of MetS cardiomyocytes underlies intrinsic dysfunctional RyR2 and SERCA pump. Abnormal activity of RyRs was evidenced by its decreased ability to bind [3H]-ryanodine. Although the MetS condition does not modify RyR2 protein expression, its phosphorylation at Ser2814 is decreased, which impairs its capacity for activation during ECC. The dysfunctional RyRs, together with a decreased activity of SERCA pump due to decreased Thr17-PLN phosphorylation suggest a downregulation of CaMKII in MetS...
Source: Frontiers in Physiology - April 29, 2019 Category: Physiology Source Type: research

Multifractal Desynchronization of the Cardiac Excitable Cell Network During Atrial Fibrillation. II. Modeling
In this study, we elaborate on a tentative interpretation of the observed intermittent dynamics during AF as the signature of synaptic plasticity. Typical individual GJC transition times between open and closed states were shown to be much longer than those of membrane polarization but compare well with membrane recovery time (≳ 100ms) (Spray et al., 1984; Neyton and Trautmann, 1986; Wang et al., 1992; Bukauskas and Verselis, 2004; Desplantez et al., 2007). Moreover, slow gating modulations have been evidenced due to cytoplasmic protons (low pH) and free calcium (Spray et al., 1984; Burt and Sray, 1988; Kumar and G...
Source: Frontiers in Physiology - April 23, 2019 Category: Physiology Source Type: research

Atrial Transcriptional Profiles of Molecular Targets Mediating Electrophysiological Function in Aging and Pgc-1 β Deficient Murine Hearts
Conclusion: These findings limit the possible roles of gene transcriptional changes in previously reported age-dependent pro-arrhythmic electrophysiologial changes observed in Pgc-1β-/- atria to an altered Ca2+-ATPase (Atp2a2) expression. This directly parallels previously reported arrhythmic mechanism associated with p21-activated kinase type 1 deficiency. This could add to contributions from the direct physiological outcomes of mitochondrial dysfunction, whether through reactive oxygen species (ROS) production or altered Ca2+ homeostasis. Introduction Atrial arrhythmias constitute a major public health pro...
Source: Frontiers in Physiology - April 23, 2019 Category: Physiology Source Type: research