Linked Life Data

9444302

Source:http://linkedlifedata.com/resource/pubmed/id/9444302

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1998-2-4
pubmed:abstractText
The role of nitric oxide in the autonomical regulation of atrioventricular (AV) spontaneous action potentials and L-type calcium current (ICa-L) in isolated single AV nodal cells from rabbit heart was examined by using the whole cell patch clamp technique, immunohistochemical staining and single cell reverse transcription polymerase chain reaction analysis. The nitric oxide donor 3-morpholino-sydnonimine (SIN-1) (0.1 mmol/L) suppressed the beta-agonist isoproterenol- (1 mumol/L) stimulated increase in ICa-L and decreased the frequency and amplitude of spontaneous action potentials. In cells in which ICa-L had been previously attenuated by the muscarinic agonist carbamylcholine (CCh, 1 mumol/L), SIN-1 had no additive effect. Intracellular dialysis with the nitric oxide synthase inhibitor N-monomethyl-L-arginine (L-NMMA, 0.5 mmol/L) blocked CCh- but not SIN-1-induced ICa-L attenuation. However, intracellular dialysis with methylene blue (20 mumol/L), which inhibits nitric oxide-mediated activation of guanylyl cyclase and cGMP production blocked the effects of both CCh and SIN-1 on ICa-L. In these cells, neither L-NMMA nor methylene blue affected the CCh-activated potassium current (IK(ACh)). Internal dialysis with cGMP (10 mumol/L) significantly inhibited isoproterenol-stimulated ICa-L without affecting IK(ACh). In AV nodal cells internally perfused with either a nonhydrolyzable cAMP analogue, 8-Br-cAMP (0.5 mmol/L), or a high concentration of cAMP (0.5 mmol/L), CCh did not inhibit ICa-L but still activated IK(ACh). CCh-induced ICa-L attenuation could be abolished or quickly reversed by the nonselective phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (20 mumol/L) but not by milrinone (5 mumol/L), which only inhibits the cGMP-inhibited phosphodiesterase isozyme (PDE3). Immunohistochemical staining identified the presence of the endothelial constitutive nitric oxide synthase (NOS3) in both single AV node cells in vitro and in cryostat sections of AV node tissue in situ. These results demonstrate that endogenous nitric oxide is involved in the muscarinic cholinergic attenuation of ICa-L in AV nodal cells; the mechanism likely involves the cGMP-stimulated phosphodiesterase.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0828-282X
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1191-201
pubmed:dateRevised
2008-4-9
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Nitric oxide regulation of atrioventricular node excitability.
pubmed:affiliation
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. xhan@bics.bwh.harvard.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review