A reporter on the set of a new film with two much− publicized stars asked them to describe the story. “It’s about the love−life of this great artist…” said the middle− aged male lead. “It’s about this beautiful model who inspires a whole generation…” said the movie queen. For an unbiased opinion the reporter went to an actress whose sole task was to serve tea in the final scene. “Well,” she said, “it’s about this waitress … “.
pH Homeostasis is subtitled Mechanisms and Control.
The preface by Dieter Haussinger explains that the mechanisms considered are at the molecular, subcellular, cellular and systemic levels. Question: is this a book about organs that tidy-up after pH spills? Answer: yes, but consideration is also given to “the role of pH in regulating important biological processes”. You see, pH is a star performer. ‥ homeostasis does not just mean “an absolute constancy of pH but implies integration of events allowing the free proton concentration in the various compartments to play its role as a physiological coordinator of biological processes”.
In one of the early chapters we read that intracellular pH plays a central role in the regulation of many aspects of cell metabolism, cell motility, secretory events, hormonal effects, proliferation‥ .These are grand claims! Question: and the evidence for a role of protons in proliferation? Answer: liver regeneration may be inhibited by amiloride. Question: is it also inhibited by frying over a low heat? Fortunately, Pouysségur et al. make everything clear in a fine chapter on a molecular genetic approach to the amiloride-sensitive Na/H antiporter. They suggest that an increase in internal pH does have a role in growth control, but a permissive one.
Another thing we learn in the early pages is that cellular pH may be influenced by proton pumps located in the inner mitochondrial membrane and in the plasma membrane and also perhaps by metabolic fluxes. Question: what is the effect of the metabolic flux? Answer: in the liver the change in intracellular concentration of di- and tri-carboxylic acids during the transition from fasted to fed state is sufficient to reduce the internal pH to near 4. Question: and does it? Answer: the cellular pH of about 7 ·2 is only abandoned under extreme conditions.
Much is made in these early chapters of the interaction between pH and membrane conductance. These speculations run along familiar lines: “Intracellular pH and cell membrane potential may play a role in the maintenance of cell volume (but) a great deal of experimental effort is needed to settle these issues”. The authors of chapter 2 comment that “all channels studied so far show an increased open probability at alkalization and a strongly decreased one at pH values below 7”. This is not quite accurate. Molluscan neurones have a measurable hydrogen ion conductance that increases with depolarization and with low intracellular pH. (Salamander oocytes behave similarly.) Unfortunately reference to this important work is omitted. You see, pH Homeostasis is about voltage-dependent hydrogen ion conductances… Drop me a line and I will send you a reprint!
Aspects of systemic pH regulation start on page 163 with an excellent chapter on the development of acid-base concepts by Bourke and Atkinson. This is followed by other good chapters on the role of CO2 transport (Piiper) and CO2/HCO3− equilibria (Gros et al.) in acid-base homeostasis. Then there are 100 pages on the mammalian kidney, all of which are clearly written and good to read. Systemic pH regulation is commonly considered to involve just two organs: the lungs, which deal with CO2, and the kidneys, which deal with HCO2− But the liver is important for lactate disposal and urea synthesis and so must play a major part in HCO3− homeostasis and thus of systemic pH. The editor himself is the first author on an interesting chapter that deals with the role of the liver; other useful chapters (by Knauf & Sachs and by Novak) describe the pancreas and the gastrointestinal tract.
