© 1997 American Heart Association, Inc.
Articles |
Direct Inhibition of Expressed Cardiac L-Type Ca2+ Channels by S-Nitrosothiol Nitric Oxide Donors
From the Section of Molecular and Cellular Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Md.
Correspondence to Eduardo Marban, MD, PhD, 844 Ross Bldg, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. E-mail marban{at}welchlink.welch.jhu.edu
Abstract NO donors have complex effects on Ca2+
currents in native cardiac cells, with reports of direct stimulation
and indirect cGMP-mediated inhibition or stimulation. To investigate
the molecular basis of these effects, we tested the effects of one
class of NO donors, S-nitrosothiols (RSNOs), on
expressed cardiovascular L-type Ca2+
channels (
1C±ß1a±2 or
1C±ß2a±2) in human
embryonic kidney (HEK293) cells. The RSNO compounds we used were
S-nitroso-N-acetylpenicillamine (SNAP, 5
to 10 nmol/L or 100 to 800 µmol/L),
S-nitrosocysteine (SNC, 100 µmol/L or 1
mmol/L), and S-nitrosoglutathione (GSNO, 1 mmol/L).
Currents were measured using whole-cell patch recordings with 2
to 10 mmol/L Ba2+ as the charge carrier. SNAP reduced
the amplitude of barium currents (IBa) through all the
subunit combinations, with an EC50 of 360 µmol/L for
1C+ß1a channels. SNC or GSNO also
inhibited IBa, albeit less potently. The
inhibitory effect of SNAP was not affected by methylene
blue (10 to 30 µmol/L) or 8-bromo-cGMP (200 to 400
µmol/L). The effects are relatively specific for Ca2+
channels, as expressed cardiac or skeletal muscle Na+
channels, which have a similar overall architecture, were barely
affected by SNAP at concentrations as high as 1 mmol/L. We
conclude that in the HEK293 expression system, the
S-nitrosothiol NO donors inhibit L-type Ca2+
channels by a mechanism independent of cGMP.
Key Words: nitric oxide • Ca2+ channel • Na+ channel • cysteine • oxidation
This article has been cited by other articles:
 |
|
 |
|
  J. W. Calvert and D. J. Lefer Myocardial protection by nitrite Cardiovasc Res, July 15, 2009; 83(2): 195 - 203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Gomez, L. Nunez, M. Vaquero, I. Amoros, A. Barana, T. de Prada, C. Macaya, L. Maroto, E. Rodriguez, R. Caballero, et al. Nitric oxide inhibits Kv4.3 and human cardiac transient outward potassium current (Ito1) Cardiovasc Res, December 1, 2008; 80(3): 375 - 384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Seddon, A. M. Shah, and B. Casadei Cardiomyocytes as effectors of nitric oxide signalling Cardiovasc Res, July 15, 2007; 75(2): 315 - 326. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-M. Li, J.-M. Yang, D.-H. Hu, F.-Q. Hou, M. Zhao, X.-H. Zhu, Y. Wang, J.-G. Li, P. Hu, L. Chen, et al. Contribution of Downregulation of L-type Calcium Currents to Delayed Neuronal Death in Rat Hippocampus after Global Cerebral Ischemia and Reperfusion J. Neurosci., May 9, 2007; 27(19): 5249 - 5259. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Nunez, M. Vaquero, R. Gomez, R. Caballero, P. Mateos-Caceres, C. Macaya, I. Iriepa, E. Galvez, A. Lopez-Farre, J. Tamargo, et al. Nitric oxide blocks hKv1.5 channels by S-nitrosylation and by a cyclic GMP-dependent mechanism Cardiovasc Res, October 1, 2006; 72(1): 80 - 89. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Heaton, M. Lei, D. Li, S. Golding, T. A. Dawson, R. M. Mohan, and D. J. Paterson Remodeling of the Cardiac Pacemaker L-Type Calcium Current and Its {beta}-Adrenergic Responsiveness in Hypertension After Neuronal NO Synthase Gene Transfer Hypertension, September 1, 2006; 48(3): 443 - 452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. V. Zima and L. A. Blatter Redox regulation of cardiac calcium channels and transporters Cardiovasc Res, July 15, 2006; 71(2): 310 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Sun, E. Picht, K. S. Ginsburg, D. M. Bers, C. Steenbergen, and E. Murphy Hypercontractile Female Hearts Exhibit Increased S-Nitrosylation of the L-Type Ca2+ Channel {alpha}1 Subunit and Reduced Ischemia/Reperfusion Injury Circ. Res., February 17, 2006; 98(3): 403 - 411. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-W. Yu, M.-Y. G Liu, R. H Kennedy, and S. J Liu Both cGMP and peroxynitrite mediate chronic interleukin-6-induced negative inotropy in adult rat ventricular myocytes J. Physiol., July 15, 2005; 566(2): 341 - 353. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Chen, J. Petranka, K. Yamamura, R. E. London, C. Steenbergen, and E. Murphy Gender differences in sarcoplasmic reticulum calcium loading after isoproterenol Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2657 - H2662. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Su, S. Zhang, J. Tse, P. M. Scholz, and H. R. Weiss Alterations in nitric oxide-cGMP pathway in ventricular myocytes from obese leptin-deficient mice Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H2111 - H2117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Groschner NO and cholinergic signalling in the heart: divergent routes to regulatory phosphorylation of the cardiac L-type Ca2+ channel Cardiovasc Res, November 1, 2003; 60(2): 223 - 225. [Full Text] [PDF]
|
|
|
|
|
|
C. E. Sears, S. M. Bryant, E. A. Ashley, C. A. Lygate, S. Rakovic, H. L. Wallis, S. Neubauer, D. A. Terrar, and B. Casadei Cardiac Neuronal Nitric Oxide Synthase Isoform Regulates Myocardial Contraction and Calcium Handling Circ. Res., March 21, 2003; 92 (5): e52 - e59. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D'Ascenzo, G. Martinotti, G. B. Azzena, and C. Grassi cGMP/Protein Kinase G-Dependent Inhibition of N-Type Ca2+ Channels Induced by Nitric Oxide in Human Neuroblastoma IMR32 Cells J. Neurosci., September 1, 2002; 22(17): 7485 - 7492. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Carabelli, M. D'Ascenzo, E. Carbone, and C. Grassi Nitric oxide inhibits neuroendocrine CaV1 L-channel gating via cGMP-dependent protein kinase in cell-attached patches of bovine chromaffin cells J. Physiol., June 1, 2002; 541(2): 351 - 366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Layland, J.-M. Li, and A. M Shah Role of cyclic GMP-dependent protein kinase in the contractile response to exogenous nitric oxide in rat cardiac myocytes J. Physiol., April 15, 2002; 540(2): 457 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Abi-Gerges, G. Szabo, A. S Otero, R. Fischmeister, and P.-F. Mery NO donors potentiate the {beta}-adrenergic stimulation of ICa,L and the muscarinic activation of IK,ACh in rat cardiac myocytes J. Physiol., April 15, 2002; 540(2): 411 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Ziolo, H. Katoh, and D. M. Bers Positive and negative effects of nitric oxide on Ca2+ sparks: influence of beta -adrenergic stimulation Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2295 - H2303. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Dittrich, J. Jurevicius, M. Georget, F. Rochais, B. K. Fleischmann, J. Hescheler, and R. Fischmeister Local response of L-type Ca2+ current to nitric oxide in frog ventricular myocytes J. Physiol., July 1, 2001; 534(1): 109 - 121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Vandecasteele, I. Verde, C. Rucker-Martin, P. Donzeau-Gouge, and R. Fischmeister Cyclic GMP regulation of the L-type Ca2+ channel current in human atrial myocytes J. Physiol., June 1, 2001; 533(2): 329 - 340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Abi-Gerges, R. Fischmeister, and P.-F. Mery G protein-mediated inhibitory effect of a nitric oxide donor on the L-type Ca2+ current in rat ventricular myocytes J. Physiol., February 15, 2001; 531(1): 117 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Stamler and G. Meissner Physiology of Nitric Oxide in Skeletal Muscle Physiol Rev, January 1, 2001; 81(1): 209 - 237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Yatani and T. J. Kamp Tails of the L-Type Ca2+ Channel : To Sense Oxygen or Not Circ. Res., September 29, 2000; 87(7): 535 - 536. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kanno, P. C. Lee, Y. Zhang, C. Ho, B. P. Griffith, L. L. Shears II, and T. R. Billiar Attenuation of Myocardial Ischemia/Reperfusion Injury by Superinduction of Inducible Nitric Oxide Synthase Circulation, June 13, 2000; 101(23): 2742 - 2748. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Pabelick, D. O. Warner, W. J. Perkins, and K. A. Jones S-nitrosoglutathione-induced decrease in calcium sensitivity of airway smooth muscle Am J Physiol Lung Cell Mol Physiol, March 1, 2000; 278(3): L521 - L527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hirakawa, M. Gericke, R. A. Cohen, and V. M. Bolotina Ca2+-dependent Cl- channels in mouse and rabbit aortic smooth muscle cells: regulation by intracellular Ca2+ and NO Am J Physiol Heart Circ Physiol, November 1, 1999; 277(5): H1732 - H1744. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. Brahmajothi and D. L. Campbell Heterogeneous Basal Expression of Nitric Oxide Synthase and Superoxide Dismutase Isoforms in Mammalian Heart : Implications for Mechanisms Governing Indirect and Direct Nitric Oxide-Related Effects Circ. Res., October 1, 1999; 85(7): 575 - 587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-L. Balligand Regulation of cardiac {beta}-adrenergic response by nitric oxide Cardiovasc Res, August 15, 1999; 43(3): 607 - 620. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hu, T. Sato, J. Seharaseyon, Y. Liu, D. C. Johns, B. O'Rourke, and E. Marbán Pharmacological and Histochemical Distinctions Between Molecularly Defined Sarcolemmal KATP Channels and Native Cardiac Mitochondrial KATP Channels Mol. Pharmacol., June 1, 1999; 55(6): 1000 - 1005. [Abstract] [Full Text]
|
|
|
|
 |
|
 B. A. Summers, J. L. Overholt, and N. R. Prabhakar Nitric Oxide Inhibits L-Type Ca2+ Current in Glomus Cells of the Rabbit Carotid Body Via a cGMP-Independent Mechanism J Neurophysiol, April 1, 1999; 81(4): 1449 - 1457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Simonsen, R. M Wadsworth, N. H. Buus, and M. J Mulvany In vitro simultaneous measurements of relaxation and nitric oxide concentration in rat superior mesenteric artery J. Physiol., April 1, 1999; 516(1): 271 - 282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Kojda and K. Kottenberg Regulation of basal myocardial function by NO Cardiovasc Res, March 1, 1999; 41(3): 514 - 523. [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. JI, B. K. FLEISCHMANN, W. BLOCH, M. FEELISCH, C. ANDRESSEN, K. ADDICKS, and J. HESCHELER Regulation of the L-type Ca2+ channel during cardiomyogenesis: switch from NO to adenylyl cyclase-mediated inhibition FASEB J, February 1, 1999; 13(2): 313 - 324. [Abstract] [Full Text]
|
|
|
|
|
|
I M Fearon, A C V Palmer, A J Balmforth, S G Ball, G Varadi, and C Peers Modulation of recombinant human cardiac L-type Ca2+ channel {alpha}1C subunits by redox agents and hypoxia J. Physiol., February 1, 1999; 514(3): 629 - 637. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-W. Sun, M. Alonso-Galicia, M. R. Taheri, J. R. Falck, D. R. Harder, and R. J. Roman Nitric Oxide-20–Hydroxyeicosatetraenoic Acid Interaction in the Regulation of K+ Channel Activity and Vascular Tone in Renal Arterioles Circ. Res., November 30, 1998; 83(11): 1069 - 1079. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Han, I. Kubota, O. Feron, D. J. Opel, M. A. Arstall, Y.-Y. Zhao, P. Huang, M. C. Fishman, T. Michel, and R. A. Kelly Muscarinic cholinergic regulation of cardiac myocyte ICa-L is absent in mice with targeted disruption of endothelial nitric oxide synthase PNAS, May 26, 1998; 95(11): 6510 - 6515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Hu and E. Marban Isoform-Specific Inhibition of L-Type Calcium Channels by Dihydropyridines Is Independent of Isoform-Specific Gating Properties Mol. Pharmacol., May 1, 1998; 53(5): 902 - 907. [Abstract] [Full Text]
|
|
|
|
 |
|
 X.-S. Wu, H. D. Edwards, and W. A. Sather Side Chain Orientation in the Selectivity Filter of a Voltage-gated Ca2+ Channel J. Biol. Chem., October 6, 2000; 275(41): 31778 - 31785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Poteser, C. Romanin, W. Schreibmayer, B. Mayer, and K. Groschner S-Nitrosation Controls Gating and Conductance of the alpha 1 Subunit of Class C L-type Ca2+ Channels J. Biol. Chem., April 27, 2001; 276(18): 14797 - 14803. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Layland, J.-M. Li, and A. M Shah Role of cyclic GMP-dependent protein kinase in the contractile response to exogenous nitric oxide in rat cardiac myocytes J. Physiol., April 15, 2002; 540(2): 457 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. U. Ahmmed, Y. Xu, P. Hong Dong, Z. Zhang, J. Eiserich, and N. Chiamvimonvat Nitric Oxide Modulates Cardiac Na+ Channel via Protein Kinase A and Protein Kinase G Circ. Res., November 23, 2001; 89(11): 1005 - 1013. [Abstract] [Full Text] [PDF]
|
|