FADING AND REBOUND OF P2X(2) CURRENTS AT MILLIMOLAR ATP CONCENTRATIONS CAUSED BY LOW PH

When ATP is applied at high concentrations (above 1 mM) to PC12 cells, it produces a rapidly desensitizing peak current followed by a reboun d of the current after termination of the ATP application. We expresse d P2X(2) receptors, which are thought to mediate the ATP currents of P C12 cells, in HEK293 cells and studied the effects of acidification on this 'fading and rebound' phenomenon. We found that the desensitizati on disappeared after adjusting the low pH (<5.0) of the millimolar ATP concentrations to a more physiological value (pH 7.3). Furthermore, t he fading and rebound could also be induced at much lower ATP concentr ations by decreasing the pH of the ATP containing application solution s. Thus, it appears this phenomenon is not caused directly by high con centrations of ATP, but is due to a concomitant acidification that occ urs when high concentrations of ATP are dissolved in only moderately b uffered application solutions.