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G protein‐mediated inhibitory effect of a nitric oxide donor on the L‐type Ca 2+ current in rat ventricular myocytes
Author(s) -
AbiGerges Najah,
Fischmeister Rodolphe,
Méry PierreFrançois
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.0117j.x
Subject(s) - ibmx , nitric oxide , medicine , endocrinology , chemistry , isoprenaline , phosphodiesterase , pertussis toxin , soluble guanylyl cyclase , snap , myocyte , phosphodiesterase inhibitor , inhibitory postsynaptic potential , cgmp dependent protein kinase , protein kinase a , forskolin , g protein , kinase , biology , signal transduction , biochemistry , stimulation , enzyme , guanylate cyclase , computer graphics (images) , computer science , cyclin dependent kinase 2
1 The role of the cGMP pathway in the modulation of the cardiac L‐type Ca 2+ current ( I Ca,L ) by nitric oxide (NO) was examined in rat ventricular myocytes. 2 The NO donors DEANO, SIN‐1, SNP, SNAP and GSNO had no significant effects on basal I Ca,L . However, DEANO (100 μM) inhibited I Ca,L after the current had been previously stimulated by either isoprenaline (Iso, 1‐10 nM), a β‐adrenergic agonist, or isobutylmethyl‐xanthine (IBMX, 10‐80 μM), a wide spectrum phosphodiesterase (PDE) inhibitor. 3 The anti‐adrenergic effect of DEANO on I Ca,L was not mimicked by other NO donors (SIN‐1, SNAP and SPNO). 4 The NO‐sensitive guanylyl cyclase inhibitor ODQ (10 μM), antagonized the inhibitory effect of DEANO on I Ca,L . Likewise, inhibitors of the cGMP‐dependent protein kinase (cG‐PK), Rp‐8‐chloro‐phenylthio‐cGMP (10 μM) and KT5823 (0.1 and 0.3 μM), also abolished the inhibitory effect of DEANO on Iso (1‐10 nM)‐stimulated I Ca,L . 5 Intracellular dialysis with exogenous cAMP (10‐100 μM) blunted the inhibitory effect of DEANO (10 and 100 μM) on I Ca,L . SNAP and SNP also had no effect on the cAMP‐stimulated I Ca,L . 6 Pre‐treatment of the myocytes with pertussis toxin (0.5 μg ml −1 , 4‐6 h at 37 °C) eliminated the inhibitory effect of DEANO (100 μM) on I Ca,L , in the presence of either Iso (0.01 and 1 nM) or IBMX (10‐80 μM). 7 These results demonstrate that DEANO produces anti‐adrenergic effects in rat ventricular myocytes. This effect of DEANO occurs in a cGMP‐dependent manner, and involves activation of cG‐PK and regulation of a pertussis toxin‐sensitive G protein.