Activation of the Na+/K+ pump current by intra- and extracellular Li ions in single guinea-pig cardiac cells

Li+ is the only ion that can replace the physiological intra-and extracellular activator cations of the Na+/K+ pump. In order to study this singular property of Li+ in some detail, the activation of the Na+/K+ pump current (I-p) by intra-and extracellular Li+ (Li-i(+); Li-o(+)) was measured in isolated guinea-pig ventricular myocytes by means of whole cell recording at 34 degrees C and a holding potential of -20 mV. I-p was identified as current blocked by dihydro-ouabain. Half-maximal I-p activation occurred at 23 mM Li-o(+) (K-0.5 value) in cells containing Na+ (50 or 100 mM) and at 73 mM Li-o(+) in myocytes containing Li+ (100 mM). The K-0.5 value of I-p activation by Li-o(+) increased with depolarisation, suggesting the transfer of 0.2 of an elementary charge across the electric field of the sacrolemma during Li-o(+)-binding. An intracellular Li+ concentration of 36 mM caused half-maximal I-p activation in cells superfused with Na+- and Li+-free media containing 1 mM K+. In Na+-free solutions, the I-p-V curve displayed a positive slope at negative membrane potentials. A negative slope at positive potentials was observed in Li+-containing media. It is concluded that Li+ is less efficacious and potent than the physiological pump activator cations. The shape of the I-p-V curves in Na+-free solutions supports the view that the cardiac Na+/K+ pump contains a channel-like structure and suggests that there are voltage-sensitive steps in the pump cycle, apart from the binding of external cations. (C) 1997 Elsevier Science B.V.