Sodium pump current measured in cardiac ventricular myocytes isolated from control and potassium depleted rabbits

The aim was to investigate cardiac muscle sodium pump function following chronic potassium depletion in rabbits.

Sodium pump current was measured using the whole cell voltage clamp technique in ventricular myocytes from control rabbits or rabbits with chronic dietary potassium depletion, under conditions designed to minimise all other electrogenic channels, pumps, and exchangers. The effects of changes in external [K+] and intracellular [Na+] were investigated. Experiments were performed on ventricular myocytes enzymatically isolated from adult rabbits, average weight 2.5 kg, which were fed either a control (n = 6), or a potassium deficient diet (n = 8) for 25 d.

Potassium depletion significantly increased the sodium pump current density recorded with 10 mM extracellular [K+] and 50 mM [Na+] in the pipette (conditions which activate an estimated 98% of the maximally available pump current), from 1.53(SEM 0.05) pA.pF-1 (control, n = 4) to 1.740(0.06) pA.pF-1 (potassium depleted, n = 4; p < 0.05). The relationship between sodium pump current and extracellular [K+] (30 mM [Na+] in pipette) showed a significant leftward shift in myocytes from potassium depleted animals, such that the Km was reduced from 1.270(0.10) (control, n = 4) to 0.72(0.11) mM (potassium depleted, n = 4; p < 0.05). The effect of varying pipette [Na+] on sodium pump current was examined in cells superfused with 5 mM [K+]. The Km was again reduced from 19.44 mM (control) to 16.91 mM (potassium depleted). The Hill coefficients for activation of the pump by potassium and sodium were essentially unchanged, as was the shape of the current-voltage relationship.

These results suggest that chronic potassium depletion results in an adaptation of the cardiac sodium pump such that pump activity can be maintained, or even enhanced, despite a fall in plasma [K+]. This adaptation is achieved by both alterations in ionic sensitivity to potassium and sodium, and an increase in maximum activity. The latter may reflect an increase in sodium pump site density. These changes are likely to account for the preservation of intracellular [K+] in cardiac muscle during chronic potassium deficiency.