Proceedings of the Physiological Society, 19–20 January 1973, Mill Hill Meeting: Communications

Abstract

) can both be altered by changes in the local conditions. The present experiments were designed to investigate if similar changes in cultured cells involve protein and RNA synthesis.Preliminary experiments showed that partial blocking of Na pumping with ethacrynic acid caused an increase in specific ouabain binding to the cells and therefore probably an increase in the Na pump density (Baker & Willis, 1970). In subsequent experiments this inductive action of ethacrynate was used to test the effects of the protein synthesis inhibitor, cycloheximide (Jamieson & Palade, 1968) and the RNA synthesis inhibitor, actinomycin D (Clarke, Love, Studzinski & Ellem, 1966 falls; adding cycloheximide causes significantly greater changes. These results are consistent with the hypothesis that protein synthesis is necessary for pump production in normal cells and in ethacrynate treated cells.Actinomycin D (1 4ug/ml. for 24 hr) produced apparently unexpected effects. When applied alone or with ethacrynate it caused an increased specific ouabain binding compared to appropriate controls. The usual explanation for this 'superinduction' effect in other enzyme systems is that actinomycin D has caused a derepression of messenger RNA (Tomkins, Levinson, Baxter & Dethlefson, 1972). The present results however are not entirely consistent with this hypothesis as (1) the extra ouabain bound in actinomycin D plus ethacrynate was not different from the sum of that produced by either drug alone, suggesting separate sites of action for the drugs, and (2) the extra ouabain bound by actinomycin D came off the membranes much more rapidly than normally.This evidence suggests that both in normal cells and in those treated with ethacrynate the production of pump sites requires protein synthesis and perhaps RNA synthesis.Supported by a British Heart Foundation grant to J.F.L. Interpretation of the parameters relating oxygen uptake to heart rate and cardiac output during submaximal exercise BY T. J. COLE and G. J. MILLER. M.R.C. Pneumoconiosis Unit, Llandough Hospital, Penarth, GlamorganThe linear relationships between oxygen uptake (TPo,) and both heart rate (fe) and cardiac output (pt) are well established (Bevegard & Shepherd, 1967). In the relationship 1702 = a-fC-C,(1 the slope (a) and intercept (c) differ between individuals and with muscle groups used (Asmussen & Hemmingsen, 1958). The Fick equation t02 = VS *fc(Ca, 02-CV,o) (2) shows that the relationship between '102 and fc is a function of stroke volume (Is) and the oxygen contents of arterial (Ca 02) and mixed venous blood (Cv, o2 a' = Ca,o2.Then from (3):and from (1): a = Ca,02. * -Thus V8 can be calculated from (9) if a and Ca, oa are known. Comparison of (8) with (2) & Wade, 1955; Bevegard, Holmgren & Jonsson, 1960; Astrand, Cuddy, Saltin & Stenberg, 1964; Damato, Galante & Smith, 1966; Grimby, Nilsson & Saltin, 1966). Thus:(i) The slope a' for pooled data was 0-184 compared with a mean C.,02 of 0-187 litre per litre of blood.(ii) The means of V8 measured by catheter studies and ...