Uncouplers & pH

Richard Kondo rkondo at ephys.ucla.edu
Fri Aug 9 11:21:29 EST 1996

Jack Owicki wrote:
> Lou Hom wrote:
> >Let's say you treat cells with an uncoupler of oxidative phosphorylation,
> >like dinitrophenol (I think that's one), so that you cause the cell to burn
> >up all kinds of fuel struggling to make some ATP.  Would you expect this to
> >decrease the surrounding pH since more CO2 would be made?  Would you expect
> >this in vivo too (for organisms as small as insects up to humans)?
> We have in some cases seen increases in the extracellular acidification
> rate of cells treated in vitro with uncouplers, using our microphysiometry
> technology.  See, e.g., the effects of CCCP on P388D1 cells in Fig. 3 of
> Parce et al. (1989) Science 246:243-247.
> I would likely attribute this effect not just to the increase of CO2
> production (like flooring the accelerator with the car in neutral), but
> also to an increase in the excretion of lactic acid as glycolysis is
> stimulated to make up the ATP deficit.

	I wonder whether extracellular acidification could occur as a 
result of proton extrusion.  The source of protons could be 
intracellular lactate, but might also be protons released during ATP 
breakdown (see Dennis et al. (1991) J Mole. Cell. Cardio. 'Protons in 
ischemia: where do they come from; where do they go?' 23:1077-86

	Also, unless an uncoupler increases oxygen consumption (and the 
TCA cycle), there would be no reason to expect increased CO2.

> There may be other metabolic effects of increasing the proton permeability
> of the plasma membrane and other intracellular membrane systems; I don't
> believe that uncouplers are terribly selective.

	CCCP is a protonophore, but is DNP?

Richard Kondo

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