The nitric oxide donor sodium nitroprusside stimulates the Na + –K + pump in isolated rabbit cardiac myocytes

Nitric oxide (NO) affects the membrane Na + –K + pump in a tissue‐dependent manner. Stimulation of intrinsic pump activity, stimulation secondary to NO‐induced Na + influx into cells or inhibition has been reported. We used the whole‐cell patch clamp technique to measure electrogenic Na + –K + pump current ( I p ) in rabbit ventricular myocytes. Myocytes were voltage clamped with wide‐tipped patch pipettes to achieve optimal perfusion of the intracellular compartment, and I p was identified as the shift in holding current induced by 100 μ m ouabain. The NO donor sodium nitroprusside (SNP) in concentrations of 1, 10, 50 or 100 μ m induced a significant increase in I p when the intracellular compartment was perfused with pipette solutions containing 10 m m Na + , a concentration near physiological levels. SNP had no effect when the pump was near‐maximally activated by 80 m m Na + in pipette solutions. Stimulation persisted in the absence of extracellular Na + , indicating its independence of transmembrane Na + influx. The SNP‐induced pump stimulation was abolished by inhibition of soluble guanylyl cyclase (sGC) with 1H‐[1,2,4]oxadiazole[4,3‐a]quinoxalin‐1‐one, by inhibition of protein kinase G (PKG) with KT‐5823 or by inhibition of protein phosphatase with okadaic acid. Inclusion of the non‐hydrolysable cGMP analogue 8 p CPT‐cGMP, activated recombinant PKG or the sGC‐activator YC‐1 in patch pipette filling solutions reproduced the SNP‐induced pump stimulation. Pump stimulation induced by YC‐1 was dependent on the Na + concentration but not the K + concentration in pipette filling solutions, suggesting an altered sensitivity of the Na + –K + pump to intracellular Na + .