Species- and tissue-dependent effects of NO and cyclic GMP on cardiac ion channels.
Biochemical studies have established the presence of a NO pathway in the heart, including sources of NO and various effectors. Several cardiac ion channels have been shown to be modified by NO, such as L-type Ca(2+), ATP-sensitive K(+), and pacemaker f-channels. Some of these effects are mediated by cGMP, through the activity of three main proteins: the cGMP-dependent protein kinase (PKG), the cGMP-stimulated phosphodiesterase (PDE2) and the cGMP-inhibited PDE (PDE3). Other effects appear independent of cGMP, as for instance the NO modulation of the ryanodine receptor-Ca(2+) channel. In the case of the cardiac L-type Ca(2+) channel current (I(Ca,L)), both cGMP-dependent and cGMP-independent effects have been reported, with important tissue and species specificity. For instance, in rabbit sinoatrial myocytes, NO inhibits the beta-adrenergic stimulation of I(Ca,L) through activation of PDE2. In cat and human atrial myocytes, NO potentiates the cAMP-dependent stimulation of I(Ca,L) through inhibition of PDE3. In rabbit atrial myocytes, NO enhances I(Ca,L) in a cAMP-independent manner through the activation of PKG. In ventricular myocytes, NO exerts opposite effects on I(Ca,L): an inhibition mediated by PKG in mammalian myocytes but by PDE2 in frog myocytes; a stimulation attributed to PDE3 inhibition in frog ventricular myocytes but to a direct effect of NO in ferret ventricular myocytes. Finally, NO can also regulate cardiac ion channels by a direct action on G-proteins and adenylyl cyclase.
Fischmeister
Rodolphe
R
INSERM U-446, Laboratoire de Cardiologie Cellulaire et Moléculaire, Faculté de Pharmacie, Université Paris-Sud, 5, Rue J.-B. Clément, F-92296 Châtenay-Malabry Cedex, France. fisch@vjf.inserm.fr
Castro
Liliana
L
Abi-Gerges
Aniella
A
Rochais
Francesca
F
Vandecasteele
Grégoire
G
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002415:Cats; D000242:Cyclic AMP / Q000737:chemistry / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000737:chemistry / Q000378:metabolism; D006331:Heart Diseases / Q000378:metabolism; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D006984:Hypertrophy; D007473:Ion Channels / Q000737:chemistry; D007477:Ions / Q000737:chemistry; D032342:Muscle Cells / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism*; D011188:Potassium / Q000737:chemistry; D011817:Rabbits; D015398:Signal Transduction; D014018:Tissue Distribution
D007473:Ion Channels; D007477:Ions; D009569:Nitric Oxide; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D006152:Cyclic GMP; D011188:Potassium; D002118:Calcium