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Functional interactions between P2X 4 and P2X 7 receptors from mouse salivary epithelia
Author(s) -
CasasPruneda Griselda,
Reyes Juan Pablo,
PérezFlores Gabriela,
PérezCornejo Patricia,
Arreola Jorge
Publication year - 2009
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2008.167395
Subject(s) - hek 293 cells , transfection , microbiology and biotechnology , receptor , chemistry , patch clamp , ethidium bromide , complementary dna , stimulation , tetraethylammonium , biophysics , biology , biochemistry , potassium , endocrinology , dna , gene , organic chemistry
Mouse parotid acinar cells express P2X 4 and P2X 7 receptors (mP2X 4 R and mP2X 7 R) whose physiological function remains undetermined. Here we show that mP2X 4 R expressed in HEK‐293 cells do not allow the passage of tetraethylammonium (TEA + ) and promote little, if any, ethidium bromide (EtBr) uptake when stimulated with ATP or BzATP. In contrast, mP2X 7 R generates slowly decaying TEA + current, sustained Na + current and promotes robust EtBr uptake. However, ATP‐activated TEA + current from acinar cells was unlike that generated by mP2X 7 R or mP2X 4 R. Functional interactions between mP2X 4 R and mP2X 7 R were investigated in HEK cells co‐transfected with different mP2X 4 : mP2X 7 cDNA ratios and using solutions containing either TEA + or Na + ions. Co‐expressed channels generated a TEA + current that displayed faster decay during ATP stimulation than mP2X 7 R alone. Moreover, cells transfected with a 2 : 1 cDNA ratio displayed decaying kinetics similar to those observed in acinar cells. Concentration–response curves in Na + ‐containing solutions were constructed for heterologously expressed mP2X 4 R, mP2X 7 R and mP2X 4 R:mP2X 7 R co‐expressions as well as acinar cells. The EC 50 values determined were 11, 220, 434 and 442 μ m , respectively. Na + currents generated by expressing mP2X 4 R or mP2X 7 R alone were potentiated by ivermectin (IVM). In contrast, IVM potentiation in acinar cells and HEK cells co‐expressing P2X 4 and P2X 7 (1 : 1 or 2 : 1 cDNA ratios) was seen only when the ATP concentration was lowered from 5 to 0.03 m m . Taken together our observations indicate a functional interaction between murine P2X 7 and P2X 4 receptors. Such interaction might occur in acinar cells to shape the response to extracellular ATP in salivary epithelia.