Interaction of intracellular ion buffering with transmembrane-coupled ion transport.

Abstract

The role of the Na/Ca exchanger in the control of cellular excitability and tension development is a subject of current interest in cardiac physiology. It has been suggested that this coupled transporter is responsible for rapid changes in intracellular calcium activity during single beats, generation of plateau currents, which control action potential duration, and control of intracellular sodium during Na/K pump suppression, which may occur during terminal states of ischemia. The actual behavior of this exchanger is likely to be complex for several reasons. First, the exchanger transports two ionic species and thus its instantaneous flux rate depends on both intracellular sodium and calcium activity. Secondly, the alteration in intracellular calcium activity, which is caused by a given transmembrane calcium flux, and which controls the subsequent exchanger rate, is a complex function of available intracellular calcium buffering. The buffers convert the ongoing transmembrane calcium fluxes into changes in activity that are a small and variable fraction of the change in total calcium concentration. Using a number of simple assumptions, we model changes in intracellular calcium and sodium concentration under the influence of Na/Ca exchange, Na/K ATPase and Ca-ATPase pumps, and passive sodium and calcium currents during periods of suppression and reactivation of the Na/K ATPase pump. The goal is to see whether and to what extent general notions of the role of the Na/Ca exchanger used in planning and interpreting experimental studies are consistent with its function as derived from current mechanistic assumptions about the exchanger. We find, for example, that based on even very high estimates of intracellular calcium buffering, it is unlikely that Na/Ca exchange alone can control intracellular sodium during prolonged Na/K pump blockade. It is also shown that Na/Ca exchange can contaminate measurements of Na/K pump currents under a variety of experimental conditions. The way in which these and other functions are affected by the dissociation constants and total capacity of the intracellular calcium buffers are also explored in detail.

Antioxidant Gallic Acid-Functionalized Biodegradable in Situ Gelling Copolymers for Cytoprotective Antiglaucoma Drug Delivery Systems

“…For the GNGA+HP groups, the intensity level was largely decreased by the pretreatment of HLE cells with antioxidant GA-functionalized biodegradable in situ gelling copolymers. It has been documented that the Na/Ca exchanger is one of the key factors in the regulation of intracellular calcium concentration . Our findings support the intracellular ROS measurements and suggest that antioxidant GA molecules of multifunctional polymer carriers interacted with Na/Ca exchanger molecules may display cytoprotective activity against hydrogen peroxide-induced oxidative stress in lens epithelial cultures.…”

Polyphenol-rich apple (Malus domestica L.) peel extract attenuates arsenic trioxide induced cardiotoxicity in H9c2 cells via its antioxidant activity

“…This is maintained by well established transporters, exchangers and carriers. 37 Alteration in calcium homeostasis has a drastic impact on cardiac cell physiology leading to cardiac failure. Due to the profound inuence of calcium on heart function, we studied the alteration in calcium in ATO-treated cells as well as modulation by apple peel extract.…”