|
|
||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Cardiology, Royal North Shore Hospital, St Leonards, Sydney, NSW 2065, Australia
2 Department of Cardiology, Gosford Hospital, Gosford, NSW 2250, Australia
3 Department of Medicine, University of Sydney, NSW 2006, Australia
4 School of Chemistry, University of Sydney, NSW 2006, Australia
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 (Ip) in rabbit ventricular myocytes. Myocytes were voltage clamped with wide-tipped patch pipettes to achieve optimal perfusion of the intracellular compartment, and Ip was identified as the shift in holding current induced by 100 µM ouabain. The NO donor sodium nitroprusside (SNP) in concentrations of 1, 10, 50 or 100 µM induced a significant increase in Ip when the intracellular compartment was perfused with pipette solutions containing 10 mM Na+, a concentration near physiological levels. SNP had no effect when the pump was near-maximally activated by 80 mM 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 8pCPT-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+.
(Received 10 March 2005;
accepted after revision 6 April 2005;
first published online 7 April 2005)
Corresponding author H. H. Rasmussen: Department of Cardiology, Royal North Shore Hospital, St Leonards, NSW 2065, Australia. Email: helger{at}med.usyd.edu.au
This article has been cited by other articles:
![]() |
M. William, E. J. Hamilton, A. Garcia, H. Bundgaard, K. K. M. Chia, G. A. Figtree, and H. H. Rasmussen Natriuretic peptides stimulate the cardiac sodium pump via NPR-C-coupled NOS activation Am J Physiol Cell Physiol, April 1, 2008; 294(4): C1067 - C1073. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. N. White, E. J. Hamilton, A. Garcia, D. Wang, K. K. M. Chia, G. A. Figtree, and H. H. Rasmussen Opposing effects of coupled and uncoupled NOS activity on the Na+-K+ pump in cardiac myocytes Am J Physiol Cell Physiol, February 1, 2008; 294(2): C572 - C578. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Kang, Y. Dempo, A. Ohashi, M. Saito, H. Toyoda, H. Sato, H. Koshino, Y. Maeda, and T. Hirai Nitric Oxide Activates Leak K+ Currents in the Presumed Cholinergic Neuron of Basal Forebrain J Neurophysiol, December 1, 2007; 98(6): 3397 - 3410. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. E. Brack, V. H. Patel, J. H. Coote, and G. A. Ng Nitric oxide mediates the vagal protective effect on ventricular fibrillation via effects on action potential duration restitution in the rabbit heart J. Physiol., September 1, 2007; 583(2): 695 - 704. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. S. Hansen, R. J. Clarke, K. A. Buhagiar, E. Hamilton, A. Garcia, C. White, and H. H. Rasmussen Alloxan-induced diabetes reduces sarcolemmal Na+-K+ pump function in rabbit ventricular myocytes Am J Physiol Cell Physiol, March 1, 2007; 292(3): C1070 - C1077. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. M. Buckalew Atrial Peptides Modify the Effect of Marinobufagenin on Sodium Pumps: Implications for Blood Pressure Control Hypertension, December 1, 2006; 48(6): 1029 - 1030. [Full Text] [PDF] |
||||
![]() |
O. V. Fedorova, N. I. Agalakova, C. H. Morrell, E. G. Lakatta, and A. Y. Bagrov ANP Differentially Modulates Marinobufagenin-Induced Sodium Pump Inhibition in Kidney and Aorta Hypertension, December 1, 2006; 48(6): 1160 - 1168. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. J. McKenna, I. Medved, C. A. Goodman, M. J. Brown, A. R. Bjorksten, K. T. Murphy, A. C. Petersen, S. Sostaric, and X. Gong N-acetylcysteine attenuates the decline in muscle Na+,K+-pump activity and delays fatigue during prolonged exercise in humans J. Physiol., October 1, 2006; 576(1): 279 - 288. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |