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Nitric oxide activates the sarcolemmal K(ATP) channel in normoxic and chronically hypoxic hearts by a cyclic GMP-dependent mechanism. J Mol Cell Cardiol 2001 Feb;33(2):331-41

Date

02/13/2001

Pubmed ID

11162137

DOI

10.1006/jmcc.2000.1305

Scopus ID

2-s2.0-0034976745   37 Citations

Abstract

Chronic myocardial hypoxia results in elevated nitric oxide (NO) production and increased current through the sarcolemmal K(ATP) channel. We hypothesized these two processes are related and determined whether NO alters the electrophysiology of Purkinje fibers obtained from rabbits (n=12/group) raised in a normoxic (F(I)O2=0.21) or hypoxic (F(I)O2=0.12) environment from birth to 9 days of age. Action potential duration (APD)(90) was shorter (112+/-3 ms v 126+/-3 ms) and maximum diastolic potential (MDP) was more negative (-84+/-2 mV v-80+/-1 mV) in hypoxic hearts compared with normoxic controls. In normoxic hearts the NO donors, S-nitrosoglutathione (GSNO) 50 microM and spermine NONOate (50 microM) shortened APD(90) and increased MDP to levels present in chronically hypoxic hearts. This effect was completely abolished by the K(ATP) channel blocker glibenclamide (3 microM) and by a nitric oxide trap, Carboxy-PTIO (100 microM). The NO carrier glutathione (50 microM) and decomposed spermine NONOate had no effect on APD(90) or MDP. GSNO had no effect in hypoxic hearts; however, when GSNO was combined with glibenclamide APD(90) increased, and MDP decreased to normoxic values. 8-Bromo cGMP (100 microM) shortened APD(90) and increased MDP to levels present in chronically hypoxic hearts. This effect was abolished by glibenclamide. A soluble guanylyl cyclase inhibitor, ODQ (10 microM), had no effect on action potentials in normoxic hearts but in hypoxic hearts resulted in an increase in APD(90) to levels present in normoxic hearts and a decrease in MDP. The effect of ODQ could not be reversed by GSNO. We conclude that NO activates the sarcolemmal K(ATP) channel in normoxic and chronically hypoxic hearts by a cyclic GMP-dependent mechanism.

Author List

Baker JE, Contney SJ, Singh R, Kalyanaraman B, Gross GJ, Bosnjak ZJ

Authors

John E. Baker PhD Professor in the Surgery department at Medical College of Wisconsin
Zeljko J. Bosnjak PhD Professor in the Medicine department at Medical College of Wisconsin
Balaraman Kalyanaraman PhD Chair, Professor in the Biophysics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Action Potentials
Animals
Animals, Newborn
Blood Pressure
Cyclic GMP
Electron Spin Resonance Spectroscopy
Electrophysiology
Female
Glutathione
Glyburide
Hypoglycemic Agents
Hypoxia
Male
Models, Biological
Neuroprotective Agents
Nitric Oxide
Nitric Oxide Donors
Nitrogen Oxides
Nitroso Compounds
Oxygen
Potassium Channels
Rabbits
S-Nitrosoglutathione
Sarcolemma
Spermine
Time Factors
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a