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Nitric oxide regulates the calcium current in isolated human atrial myocytes.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 1995 Feb; Vol. 95 (2), pp. 794-802. - Publication Year :
- 1995
-
Abstract
- Cardiac Ca2+ current (ICa) was shown to be regulated by cGMP in a number of different species. Recently, we found that the NO-donor SIN-1 (3-morpholino-sydnonimine) exerts a dual regulation of ICa in frog ventricular myocytes via an accumulation of cGMP. To examine whether NO also regulates Ca2+ channels in human heart, we investigated the effects of SIN-1 on ICa in isolated human atrial myocytes. An extracellular application of SIN-1 produced a profound stimulatory effect on basal ICa at concentrations > 1 pM. Indeed, 10 pM SIN-1 induced a approximately 35% increase in ICa. The stimulatory effect of SIN-1 was maximal at 1 nM (approximately 2-fold increase in ICa) and was comparable with the effect of a saturating concentration (1 microM) of isoprenaline, a beta-adrenergic agonist. Increasing the concentration of SIN-1 to 1-100 microM reduced the stimulatory effect in two thirds of the cells. The stimulatory effect of SIN-1 was not mimicked by SIN-1C, the cleavage product of SIN-1 produced after liberation of NO. This suggests that NO mediates the effects of SIN-1 on ICa. Because, in frog heart, the stimulatory effect of SIN-1 on ICa was found to be due to cGMP-induced inhibition of cGMP-inhibited phosphodiesterase (cGI-PDE), we compared the effects of SIN-1 and milrinone, a cGI-PDE selective inhibitor, on ICa in human. Milrinone (10 microM) induced a strong stimulation of ICa (approximately 150%), demonstrating that cGI-PDE controls the amplitude of basal ICa in this tissue. In the presence of milrinone, SIN-1 (0.1-1 nM) had no stimulatory effect on ICa, suggesting that the effects of SIN-1 and MIL were not additive. We conclude that NO may stimulate ICa in human atrial myocytes via inhibition of the cGI-PDE.
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Animals
Anura
Calcium Channels drug effects
Cells, Cultured
Cyclic GMP physiology
Dose-Response Relationship, Drug
Female
Heart drug effects
Heart physiopathology
Heart Atria
Humans
Isoproterenol pharmacology
Kinetics
Male
Membrane Potentials drug effects
Middle Aged
Milrinone
Molsidomine pharmacology
Patch-Clamp Techniques
Pyridones pharmacology
Time Factors
Calcium Channels physiology
Heart physiology
Molsidomine analogs & derivatives
Nitric Oxide physiology
Vasodilator Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9738
- Volume :
- 95
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 7860763
- Full Text :
- https://doi.org/10.1172/JCI117729