Effect of Ion Concentration Changes in the Limited Extracellular Spaces on Sarcolemmal Ion Transport and Ca2+ Turnover in a Model of Human Ventricular Cardiomyocyte

Abstract

We have developed a computer model of human cardiac ventricular myocyte (CVM), including t-tubular and cleft spaces with the aim of evaluating the impact of accumulation-depletion of ions in restricted extracellular spaces on transmembrane ion transport and ionic homeostasis in human CVM. The model was based on available data from human CVMs. Under steady state, the effect of ion concentration changes in extracellular spaces on [Ca2+]i-transient was explored as a function of critical fractions of ion transporters in t-tubular membrane (not documented for human CVM). Depletion of Ca2+ and accumulation of K+ occurring in extracellular spaces slightly affected the transmembrane Ca2+ flux, but not the action potential duration (APD90). The [Ca2+]i-transient was reduced (by 2%–9%), depending on the stimulation frequency, the rate of ion exchange between t-tubules and clefts and fractions of ion-transfer proteins in the t-tubular membrane. Under non-steady state, the responses of the model to changes of stimulation frequency were analyzed. A sudden increase of frequency (1–2.5 Hz) caused a temporal decrease of [Ca2+] in both extracellular spaces, a reduction of [Ca2+]i-transient (by 15%) and APD90 (by 13 ms). The results reveal different effects of activity-related ion concentration changes in human cardiac t-tubules (steady-state effects) and intercellular clefts (transient effects) in the modulation of membrane ion transport and Ca2+ turnover.

Pathological transitions in myelin membranes driven by environmental and multiple sclerosis conditions

“…The concentration of the ions mentioned above can vary globally and locally. Cation concentration may change during diseased state ( 38 – 42 ) and locally can be either very low or high. More importantly, varying the cation concentration can highlight differences between the cation’s role in modifying the membrane structure.…”

Non-ventricular, Clinical, and Functional Features of the RyR2R420Q Mutation Causing Catecholaminergic Polymorphic Ventricular Tachycardia

“…First, our findings clearly reflect that the RyR2 R420Q mutation behaves as a gain-of-function both in permeabilized and intact cells ( Figures 5D, 5F, 6E and 6F) at very low [Ca 2+ ] i , similar to that measured in rat and human cardiomyocytes. 46,47 Second, the reason for the reduced peak of caffeine-evoked [Ca 2+ ] release in RyR2 R420Q cells ( Figure 5E) does not have a straightforward interpretation. It could be related to a hypoactive channel at higher cytosolic Ca 2+ but without significant shift in EC 50 .…”

“…19 Genetic Work-up DNA was obtained from whole blood (relatives) or from paraffin-embedded myocardium (proband). Targeted mutational RyR2 analysis (direct sequencing of exons 3,8,14,15,37,[44][45][46][47][48][49][50]83, 87-105, and adjacent intronic regions, GenBank accession number NM_001035) with an ABI Prism 3100 sequencer (Applied Biosystems) in individual III:10 identified the RyR2 R420Q mutation and exon 14 was sequenced in the remaining relatives (mutation carriers were considered genotype+). Since Andersen Tawil syndrome is characterized by a normal or near-normal QTc, giant U waves and polymorphic exercise-related VA due to mutations in KCNJ2 gene, this gene was also sequenced in CPVT individuals.…”

Kappa-Carrageenan-Based Dual Crosslinkable Bioink for Extrusion Type Bioprinting

“…The shear-thinning and ionic crosslinking property of κ-CA is suitable as a bioink for extrusion-based bioprinting systems. However, the κ-CA hydrogel formed solely by ionic bonding may become unstable under physiological condition as frequent ion concentration changes may take place in extracellular spaces [ 15 ]. To compensate for this limitation, the substitution of the hydroxyl group (-OH) of κ-CA with methacrylic group of MA enables photopolymerization, thereby enhancing the stability of the molecular structure [ 12 ].…”