br Acknowledgements br Introduction This article similar

Acknowledgements
Introduction This article, similar to those before [1,2], presents a selection of nails for those red blood cell physiologists with hammers. The various topics are not necessarily lost for, like occupants on a carousel, they reappear periodically. Sometimes, however, some articles seem to have been written in invisible ink for the findings reappear de novo unaware of previous studies. This, of course, reflects a diminished interest in searching or familiarity with the past. The hope inherent with this article, with limited coverage of the mentioned topics, is to stimulate interest in thinking about important aspects of red cell properties, like those previously mentioned, which should, in my opinion, not be lost.
Control of red blood cell Na and associated properties While the intracellular content of Na+ + K+ controls the water content and therefore red cell volume (e.g., [3]) it has yet to be established what cellular membrane mechanisms underlie this control. Excluding carnivores, red cell Na+ in mammals is primarily modulated by the Na+/K+ pump balancing the influx of Na+ that occurs by various means. Na+ transport into the cell happens mainly by electrodiffusion but can also occur by Na+/PO42− transport [4], ion pair formation/cotransport [5], by Na+/H+ exchange [6,7] and by NaK2Cl co-transport [8,9]. It would be of interest to know just what the contribution/activity each of these mechanisms have to the intracellular Na+ concentration under physiological circumstances, i.e., red Nocodazole receptor in their normal gas-containing plasma at 37 °C. (see [10]). One wonders how Na+ transport (and metabolism) might change or be influenced in diseased states, altered acid/base balance or variations in plasma Na+. Alterations in plasma phosphate levels could alter the Na+ pump activity either directly or by affecting the compartmental concentration of ATP contained in the membrane pool that fuels the Na+ pump [11]. It is not known whether the cell's Ca2+ pump is also affected. Cell volume changes that occur during flow from arterial to venus circulation or through the renal papilla are presumably too transient to effectively alter intracellular Na+. A different level of complexity concerns the molecular mechanisms that define the number of Na+/K+ pumps in the mature red blood cell membrane. It is known that the number of pumps in immature cells (e.g. erythroid progenitors) exceeds the number found in mature cells but the genetic control mechanisms that are involved are unknown. So too are the mechanisms for Na+/K+ pump degradation during maturation of reticulocytes [12,13]. The number of red cell Na+/K+ pumps in normal individuals is known to vary by a factor of 3 to 4 that results in an inverse correlation with the cellular control of Na+ ([14] p. 38). The contribution of the various factors mentioned above to the slope of this relationship is unknown.
Divisive topics It is always curious when a misleading title of an article appears in the literature but none more flawed than one claiming the demise of the “perfect” osmometric properties of human red blood cells [15]. The authors claim that because exposure to certain agents induces a regulated volume decrease (RVD) that red cells can no longer be considered perfect osmometers. Unfortunately, their findings and arguments are in fact irrelevant because they fail to address the issue directly or indirectly, particularly with normal unaltered cells. It is also interesting how terms creep into the literature such as “suicidal death” of red blood cells and “eryptosis” (e.g., [16,17]). Serious science has historically excluded the use of anthropomorphic terms and concepts. “Eryptosis” erroneously implies an analogy with apoptosis, a nuclear and mitochondrial event. There is no need for presumed laboratory jargon to appear in the literature when relevant and accepted terms are historically already in use.