NDLI: Role of the NO-cGMP cascade in regulation of L-type Ca$^{2+}$ currents in isolated cardiomyocytes

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Role of the NO-cGMP cascade in regulation of L-type Ca$^{2+}$ currents in isolated cardiomyocytes

Content Provider	Springer Nature Link
Author	Grushin, K. S. Nev, M. N. Dynnik, V. V. Semushina, S. G. Pakhomova, I. A. Murashev, A. N. Kokoz, Yu. M.
Copyright Year	2008
Abstract	Regulatory mechanisms of voltage-dependent L-type Ca$^{2+}$ channels involving the cyclic nucleotide system of mammalian cardiomyocytes have been studied. Activation of cGMP-dependent phosphorylation in the presence of 1 mM arginine in all experimental media resulted in inhibition of amplitudes of basal L-type Ca$^{2+}$ currents in rat ventricular myocytes. Effects of compounds regulating the activity of different compoments of the NO-cGMP cascade on L-type Ca$^{2+}$ currents were investigated. It was found that endogenous (arginine, 5 mM) and exogenous (sodium nitroprusside, 1 mM) NO sources decreased the Ca$^{2+}$ current amplitude by 30 ± 10%. The nonspecific NO synthase blocker 7NI (2 μM) abolished the effect of arginine, while the soluble guanylyl cyclase blocker ODQ (50 μM) eliminated the effects of both arginine and sodium nitroprusside. The fact that inhibitory effects of arginine, sodium nitroprusside and 8Br-cGMP disappeared in the presence of the protein kinase G blocker KT5823 (0.5, 1 μM) provides direct evidence in favor of activating effect of these compounds on PKG-dependent phosphorylation. Inhibition of L-type Ca$^{2+}$ currents can also be due to activation of phosphodiesterase II. However, the selective phosphodiesterase II blocker EHNA (30 μM) failed to abolish inhibitory effects of arginine and sodium nitroprusside on Ca$^{2+}$ currents. Isoproterenol (0.1 μM)-activated L-type Ca$^{2+}$ currents were only partly blocked by acetylcholine (0.1 mM). Contrary to basal currents, the NO-cGMP cascade agonists arginine and sodium nitroprusside (SNP), like 8Br-cGMP, had no effect on isoproterenol-induced currents. Full inhibition of isoproterenol-induced currents was achieved through combination of acetylcholine with NO-cGMP cascade agonists.
Starting Page	243
Ending Page	252
Page Count	10
File Format	PDF
ISSN	19907478
Journal	Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology
Volume Number	2
Issue Number	3
e-ISSN	19907494
Language	English
Publisher	SP MAIK Nauka/Interperiodica
Publisher Date	2008-08-29
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cell Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Biophysics

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