Influence of organic acids on intracellular pH

Abstract

By use of double-barreled pH-sensitive microelectrodes, intracellular pH was measured in isolated sheep cardiac Purkinje strands. After equimolar substitution of 20 mmol/l Cl- by several organic anions at constant extracellular pH 6.8, the rate of induced intracellular acidification was measured. For many organic acids tested, a relation was found between the rate of intracellular acidification and the product of their dissociation constant (pK'a) and diisopropylether-to-water partition ratio (p'). L-Lactate and pyruvate, and also cyanoacetate and alpha-ketobutyrate, caused faster acidifications than anticipated from their pK'a and p'. The rate of intracellular acidification, induced by L-lactate and pyruvate, was markedly depressed in the presence of 4 mmol/l alpha-cyano-4-hydroxycinnamate, a known inhibitor of the carrier-mediated pyruvate transport. The drug also had an effect on the acidification produced by cyanoacetate, alpha-ketobutyrate, glycolate, alpha-hydroxybutyrate, and alpha-chloropropionate, but not on that produced by propionate and acetate. L-Lactate caused a faster acidification than D-lactate. Our results suggest the existence of a facilitated diffusion for L-lactate, pyruvate, and some other organic acids in sheep Purkinje cells.

The role of bicarbonate in GABAA receptor‐mediated IPSPs of rat neocortical neurones.

“…4 shown to induce a fall in pHi (Sharp & Thomas, 1981;Roos & Boron, 1981;De Hemptinne, Marrannes & Vanheel, 1983;Szatkowski & Thomas, 1989 advantage since a low extracellular pH has been shown to impair proton extrusion across neuronal plasma membranes (Jean, Frelin, Vigne, Barbry & Lazdunski, 1985).…”

“…A further complication which precluded the use of ammonia in the present work is its capability to inhibit K+-Cl-co-transport (Aickin et al 1982;Thompson et al 1988 b). Lactate was chosen in the present experiments because it permeates cell membranes in its protonated form by both passive and facilitated diffusion (Spencer & Lehninger, 1976;De Hemptinne et al 1983;Mason et al 1990). Both mechanisms promote a fall in pH1 upon exposure of a cell to a lactate-containing solution.…”

Metabolic changes during ischaemia and their role in contractile failure in isolated ferret hearts.

“…An 470 CAUSES OF ISCHAEMIC CONTRACTILE FAILURE alternative is to try to mimic the metabolic changes accompanying ischaemia in a model with continued perfusion. Exposure to CN-leads to an increase in [Pi]i, but only to a small intracellular acidosis (Allen et al 1985;Eisner et al 1987b evidence suggests that in cardiac muscle much of this transport of lactate and protons is mediated by a lactate-proton co-transporter which can be partially blocked by cinnamate derivatives (de Hemptinne, Marrannes & Vanheel, 1983;Trosper & Philipson, 1987). Figure 3 shows an experiment in which a heart was exposed to CN-in the absence and subsequently in the presence of x-cyano-4-hydroxycinnamic acid (CHC) and 40 mM).…”

“…The effects of a-cyano-4-hydroxycinnamate ca-Cyano-4-hydroxycinnamate (CHC) has been reported to inhibit the transport of lactate and some other anions across the cardiac sarcolemma (de Hemptinne et al 1983;Mann, Zlokovic & Yudilevich, 1985;Trosper & Philipson, 1987;Poole, Halestrap, Price & Levi, 1989), and experiments on rat hearts have shown that lactate efflux during exposure to CN-in rat hearts is inhibited by CHC (Eisner, Peckett & Ware, 1988). CHC had relatively little effect on developed pressure and pHi under control (aerobic) conditions, when the rate of lactate production by glycolysis will be minimal (see e.g.…”

Lactate-Containing Peritoneal Dialysis Solutions

“…The lactic acid molecule so produced presumably can enter cells through the process of non-ionic diffusion (followed by subsequent dissociation of the acid inside the cells) (6,7), or through a carriermediated cotransport system for the lactate anion and a proton (7,8). As a result, a prompt and severe intracellular acidosis is generated (9,10) (Fig.…”