Cellular Sodium pumping

It has been suggested that alterations in cellular sodium pumping (page 198) may be involved in the regulation of energy balance but it has not been clearly demonstrated that there is a lower rate of pumping in obese subjects. 

Muscle activity is accompanied by cellular pumping of sodium ions. The energy requirements of the sodium pump have been studied on an individual cardiac muscle mounted inside a tiny differential calorimeter and stimulated by electrical impulses. The heat evolved was different in the presence and absence of a known inhibitor of the sodium pump. 

This simple experiment was important in that it clearly established the key notion that cellular extrusion of sodium ions by the sodium pump was coupled to metabolism. Because in this and subsequent experiments of the same sort the electrochemical gradient for sodium was known precisely, and since the fluxes of sodium (and later potassium) both into and out of the cell could be measured independently, this study also laid the groundwork for a theoretical definition of active transport, a theory worked out independently by Ussing in the flux ratio equation for transepithelial active transport of ions (see below). 

This pioneering work showed that the sodium pump was not confined to the plasma membrane of excitable cells (the pump is in fact found in virtually all animal cells) it also paved the way for an avalanche of mechanistic studies examining very many aspects of the function of the sodium pump. These included partial reactions, kinetic affinities for the three substrates at both sides of the membrane and their mutual interdependence, ATP utilization and its stoichiometric relationship to cation fluxes. Such experiments were readily performed on the red cell since these are available in large quantities and the development of simple technical procedures such as red cell ghost formation by transient hypotonic shock allowed ready access to, and control of, the intra- as well as extra-cellular face of the pump. 

Perhaps the main peroxide-induced alterations, within cells and tissues, are those that affect calcium and sodium homeostasis. Na, K-ATPase, which is considered as the core of the sodium pump , is strongly affected by peroxides, and especially by lipid hydroperoxides [137-139]. This implies that oxidative stress will usually be associated with cellular edema . Alternatively, activation of the Na, K-ATPase of vascular endothelia, such as the blood-brain barrier, will result in extracellular edema on the antiluminal side of the endothelium, due to massive influx of sodium ions [119]. 

This section will start with a short review of the functioning of the sodium pump and then examine the main evidence supporting an action of the toxin in the sodium pump or in other cellular targets. 

Research on palytoxin effects generally relates to two major areas. A broad range of studies focuses on how palytoxin regulates ion flux, which is the first effect of this toxin on the cell. Another broad class of studies concentrates on several cellular effects elicited by the toxin such as tumor promotion. The vast majority of work performed to test the mechanism of action of palytoxin has relied on the initial experiments indicating PTX binding to Na , K -ATPase therefore, this section will examine the main evidences supporting an action of the toxin in the sodium pump and continue with the effects of the toxin in other cellular targets. 

Chapter 6. THE SODIUM PUMP IN ANIMAL TISSUES AND ITS ROLE IN THE CONTROL OF CELLULAR METABOLISM P. F. Baker... 

Corneal erxlothellum is a single cellular layer with high adenosine triphosphatase (ATPase) content. It supports active transport ard the sodium pump that assists in proper hydration of the cornea. 

Thus, it appears that a normal complement of the final virion structural polypeptides El, E2, and C is not required for the cellular protein inhibition, although intermediate cleavage products or an uncleaved precursor polypeptide may be involved. Which virus-specific polypeptide is responsible for damaging the sodium pump and altering the permeability of the host cell membrane can only be determined by further experimentation. 

A sustained inhibition of the Na/K pump following a period of oxidant stress would be expected to raise intracellular sodium and favour calcium influx via the Na/Ca exchanger. Ischaemia and reperflision-induced oxidant stress, therefore, may result in a loss of Na/K pump activity, an eflFect that may involve free-radical-mediated changes in cellular thiol status. 

Sodium and potassium are not the only ions which can participate in pumps and channels. Calcium is also pumped, channeled, exhanged,and stored. See Figure 23. Calcium concentration within the cell cytoplasm is very low. This allows the calcium to play a pivotal role in cellular activity. The cytoplasmic protein calmodulin binds and stores calcium ion. Various intracellular structures and organelles such as the mitochondria and sarcoplasmic reticulum also store calcium. Calcium is vital to such functions as the release of neurotransmitters from nerve cells. There are at least seven known modes of biochemical action for this ion, one of the most important of which involves stimulation of cardiac muscle protein (actin-myosin). Certain types of angina (heart pain) are believed to be caused by abnormal stimulation of cardiac arteries and muscle (coronary spasm) A relatively new class of drugs, known as the calcium channel blockers, has brought relief from pain and arrhythmias (irregular heart beats). 

---