Recurrent atrial myxoma, right atriotomy, and sinus node dysfunction: A case of interdisciplinary care

Primary cardiac tumors are rare, and atrial myxomas represent about half of the benign tumors encountered. When found, definitive treatment is surgical resection. Following resection of these tumors, recurrence is possible, and these patients need regular follow-up. In the case of recurrence, repeat surgical intervention is feasible, but the potential for more disruption in atrial anatomy has to be considered. This could contribute to cardiac arrhythmias, and anticipation of these events is necessary to optimize patient care. We present the case of a woman with a recurrent left atrial myxoma who developed sinus node dysfunction after resection and discuss her clinical management

Control of Gastric H,K-ATPase Activity by Cations, Voltage and Intracellular pH Analyzed by Voltage Clamp Fluorometry in Xenopus Oocytes

Whereas electrogenic partial reactions of the Na,K-ATPase have been studied in depth, much less is known about the influence of the membrane potential on the electroneutrally operating gastric H,K-ATPase. In this work, we investigated site-specifically fluorescence-labeled H,K-ATPase expressed in Xenopus oocytes by voltage clamp fluorometry to monitor the voltage-dependent distribution between E1P and E2P states and measured Rb+ uptake under various ionic and pH conditions. The steady-state E1P/E2P distribution, as indicated by the voltage-dependent fluorescence amplitudes and the Rb+ uptake activity were highly sensitive to small changes in intracellular pH, whereas even large extracellular pH changes affected neither the E1P/E2P distribution nor transport activity. Notably, intracellular acidification by approximately 0.5 pH units shifted V0.5, the voltage, at which the E1P/E2P ratio is 50∶50, by −100 mV. This was paralleled by an approximately two-fold acceleration of the forward rate constant of the E1P→E2P transition and a similar increase in the rate of steady-state cation transport. The temperature dependence of Rb+ uptake yielded an activation energy of ∼90 kJ/mol, suggesting that ion transport is rate-limited by a major conformational transition. The pronounced sensitivity towards intracellular pH suggests that proton uptake from the cytoplasmic side controls the level of phosphoenzyme entering the E1P→E2P conformational transition, thus limiting ion transport of the gastric H,K-ATPase. These findings highlight the significance of cellular mechanisms contributing to increased proton availability in the cytoplasm of gastric parietal cells. Furthermore, we show that extracellular Na+ profoundly alters the voltage-dependent E1P/E2P distribution indicating that Na+ ions can act as surrogates for protons regarding the E2P→E1P transition. The complexity of the intra- and extracellular cation effects can be rationalized by a kinetic model suggesting that cations reach the binding sites through a rather high-field intra- and a rather low-field extracellular access channel, with fractional electrical distances of ∼0.5 and ∼0.2, respectively

Energy & Environmental Benefits from Steam & Electricity Cogeneration

Eastman's Texas Operations (TEX) occupies a 6,000 acre site where it manufactures more than 60 major products and employs 1,800 persons in a complex of more than 200 buildings. TEX is Eastman's largest single consumer of energy; its processes require la

Molecular mechanisms of K+ selectivity in Na/K pump

The sodium–potassium (Na/K) pump plays an essential role in maintaining cell volume and secondary active transport of other solutes by establishing the Na+ and K+ concentration gradients across the plasma membrane of animal cells. The recently determined crystal structures of the Na/K pump to atomic resolution provide a new impetus to investigate molecular determinants governing the binding of Na+ and K+ ions and conformational transitions during the functional cycle. The pump cycle is generally described by the alternating access mechanism, in which the pump toggles between different conformational states, where ions can bind from either the intracellular or the extracellular side. However, important issues concerning the selectivity of the Na/K pump remain to be addressed. In particular, two out of the three binding sites are shared between Na+ and K+ and it is not clear how the protein is able to select K+ over Na+ when it is in the outwardly facing phosphorylated conformation (E2P), and Na+ over K+ when it is in the inwardly facing conformation (E1). In this review article, we will first briefly review the recent advancement in understanding the microscopic mechanism of K+ selectivity in the Na/K pump at the E2.Pi state and then outline the remaining challenges to be addressed about ion selectivity

Selectivity of externally facing ion-binding sites in the Na/K pump to alkali metals and organic cations

The Na/K pump is a P-type ATPase that exchanges three intracellular Na+ ions for two extracellular K+ ions through the plasmalemma of nearly all animal cells. The mechanisms involved in cation selection by the pump's ion-binding sites (site I and site II bind either Na+ or K+; site III binds only Na+) are poorly understood. We studied cation selectivity by outward-facing sites (high K+ affinity) of Na/K pumps expressed in Xenopus oocytes, under voltage clamp. Guanidinium+, methylguanidinium+, and aminoguanidinium+ produced two phenomena possibly reflecting actions at site III: (i) voltage-dependent inhibition (VDI) of outwardly directed pump current at saturating K+, and (ii) induction of pump-mediated, guanidinium-derivative–carried inward current at negative potentials without Na+ and K+. In contrast, formamidinium+ and acetamidinium+ induced K+-like outward currents. Measurement of ouabain-sensitive ATPase activity and radiolabeled cation uptake confirmed that these cations are external K+ congeners. Molecular dynamics simulations indicate that bound organic cations induce minor distortion of the binding sites. Among tested metals, only Li+ induced Na+-like VDI, whereas all metals tested except Na+ induced K+-like outward currents. Pump-mediated K+-like organic cation transport challenges the concept of rigid structural models in which ion specificity at site I and site II arises from a precise and unique arrangement of coordinating ligands. Furthermore, actions by guanidinium+ derivatives suggest that Na+ binds to site III in a hydrated form and that the inward current observed without external Na+ and K+ represents cation transport when normal occlusion at sites I and II is impaired. These results provide insights on external ion selectivity at the three binding sites