Electrogenic Li+/Li+ exchange mediated by the Na+-K+ pump in rabbit cardiac myocytes

The membrane Na+-K+ pump can be activated at extracellular sites by several different monovalent cations, including Li+, while being highly selective for the physiological activator Na+ at intracellular sites. We examined whether Li+ can replace Na+ as an activator of the Na+-K+ pump at intracellular sites. Single cardiac myocytes were voltage clamped at 0 mV with wide-tipped patch pipettes filled with a K+- and Na+-free solution containing 160 mM Li+. Ouabain induced an inward shift of membrane current when the myocytes were superfused with Na+-Tyrode solution containing 5.6 mM K+. The shift was dependent on the presence of intracellular Li+ (LiCl in pipette filling solution replaced with tetramethylammonium chloride) and extracellular K+. When we replaced Na+ and K+ in the superfusate with Li+ and voltage clamped myocytes using Li+-containing filling solutions in patch pipettes, ouabain induced an inward shift in membrane current similar to that recorded when myocytes were superfused with K+-containing Na+-Tyrode solution. These findings indicate that the Na+-K+ pump can mediate electrogenic exchange of intracellular Li+ for extracellular K+ or Li+.