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Cellular responses to external ATP which precede an increase in nucleotide permeability in transformed cells
Author(s) -
Weisman Gary A.,
De Barun K.,
Friedberg Ilan,
Pritchard Robert S.,
Heppel Leon A.
Publication year - 1984
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041190211
Subject(s) - intracellular , ouabain , nucleotide , permeability (electromagnetism) , biophysics , efflux , membrane permeability , atpase , biochemistry , chemistry , divalent , membrane , microbiology and biotechnology , biology , enzyme , sodium , organic chemistry , gene
Abstract Transformed mouse fibroblasts, such as 3T6, exhibit an increase in plasma membrane permeability to nucleotides and other normally impermeant molecules when incubated with external ATP in an alkaline medium low in divalent cations. Increased nucleotide permeability, induced by external ATP, occurs after a 3‐ to 5‐min lag period. Prior to this event, there is a dramatic Na + influx and K + efflux, a significant reduction in the levels of intracellular ATP and organic phosphates, and a reduction in the plasma membrane potential. Accordingly, we postulate that these cellular responses to external ATP play a role in the efflux of nucleotides. Ouabain, a specific inhibitor of the plasma membrane (Na + , K + )‐ATPase, acts together with low concentrations of external ATP to increase nucleotide permeability in 3T6 cells. This effect occurs at concentrations of ouabain and ATP which alone do not increase nucleotide permeability. In addition, ouabain and low concentrations of ATP alone have little effect on the level of intracellular ATP. This is in contrast to energy inhibitors and uncouplers which appear to enhance nuclectide permeability by lowering the intracellular ATP concentration. Ouabain alone causes a threefold increase in intracellular Na + levels and a similar reduction in intracellular K + levels under our experimental conditions, supporting the idea that ion fluxes are involved in the mechanism of permeabilization.