CHANGE OF APPARENT STOICHIOMETRY OF PROXIMAL-TUBULE NA-HCO3- COTRANSPORT UPON EXPERIMENTAL REVERSAL OF ITS ORIENTATION()

Electrogenic cotransport of Na+ with HCO3- has been reported in numero us tissues. It has always been shown with a net transfer of negative c harge, but in some situations achieves net outward transport of both s pecies with a stoichiometry of at least three HCO3- ions per Na+ ion ( 3:1), and in other situations achieves net inward transport of both sp ecies and has a stoichiometry of at most two HCO3- ions per Na+ ion (2 :1). This suggests either that there may be more than one protein resp onsible for Na+-HCO3- cotransport in different tissues or that if ther e is a single protein, its stoichiometry may differ depending on the o rientation of net transport. The present study, using conventional or double-barreled ion-selective microelectrodes to follow basolateral me mbrane potential and intracellular pH or Na+ activity in Necturus prox imal convoluted tubule in vivo, shows that the orientation of the baso lateral Na+-HCO3- cotransporter can be reversed upon switching from a perfusate simulating normal acid-base conditions to one that imposes p eritubular isohydric hypercapnia. Moreover, accompanying the reversal of orientation is a change of apparent stoichiometry from 3:1 to 2:1. Given that the observed change of orientation and accompanying change of apparent stoichiometry occur within seconds and in the same prepara tion, these results suggest that a single transport protein is respons ible for both types of behavior.