Voltage-gated calcium channel currents in human coronary myocytes. Regulation by cyclic GMP and nitric oxide.

Quignard, Jean-François; Frapier, Jean Marc; Harricane, Marie-Cécile; Albat, Bernard; Nargeot, Joël; Richard, Sylvain

doi:10.1172/jci119146

Cited by 78 publications

(55 citation statements)

References 45 publications

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“…cGMP accumulation has been shown to decrease cardiac contractility via reduction of myofilament sensitivity to calcium. 46,47 In addition, we observed increased eNOS expression in both strains treated with DOCA-salt, which tended to be greater in iNOSϪ/Ϫ (Pϭ0.05). Increased eNOS expression may be a compensatory mechanism for increased vascular resistance and decreased myocardial perfusion.…”

Section: Sun Et Al Role Of Inos In Doca-salt Hypertension 1359mentioning

confidence: 71%

Lack of Inducible NO Synthase Reduces Oxidative Stress and Enhances Cardiac Response to Isoproterenol in Mice With Deoxycorticosterone Acetate–Salt Hypertension

et al. 2005

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Abstract-Although NO derived from endothelial NO synthase (eNOS) is thought to be cardioprotective, the role of inducible NO synthase (iNOS) remains controversial. Using mice lacking iNOS (iNOSϪ/Ϫ), we studied (1) whether development of hypertension, cardiac hypertrophy, and dysfunction after deoxycorticosterone acetate (DOCA)-salt would be less severe compared with wild-type controls (WT; C57BL/6J), and (2) whether the cardioprotection attributable to lack of iNOS is mediated by reduced oxidative stress. Mice were uninephrectomized and received either DOCA-salt (30 mg/mouse SC and 1% NaClϩ0.2% KCl in drinking water) or vehicle (tap water) for 12 weeks. Systolic blood pressure (SBP) was measured weekly. Left ventricular (LV) ejection fraction (EF) by echocardiography and cardiac response to isoproterenol (50 ng/mouse IV) were studied at the end of the experiment. Expression of eNOS and iNOS as well as the oxidative stress markers 4-hydroxy-2-nonenal (4-HNE, a marker of lipid peroxidation) and nitrotyrosine (a marker for peroxynitrite) were determined by Western blot and immunohistochemical staining, respectively. DOCA-salt increased SBP and LV weight similarly in both strains and decreased EF in WT but not in iNOSϪ/Ϫ. Cardiac contractile and relaxation responses to isoproterenol were greater, 4-HNE and nitrotyrosine levels were lower, and eNOS expression tended to be higher in iNOSϪ/Ϫ. We conclude that lack of iNOS leads to better preservation of cardiac function, which may be mediated by reduced oxidative stress and increased eNOS; however, it does not seem to play a significant role in preventing DOCA-salt-induced hypertension and hypertrophy. Key Words: nitric oxide synthase Ⅲ cardiac function Ⅲ oxidative stress N itric oxide is synthesized from L-arginine by 3 isoforms of NO synthase (NOS), described as neuronal (nNOS), inducible (iNOS), and endothelial (eNOS). In the heart, eNOS and nNOS are constitutively expressed in the endocardium, vascular endothelium, and cardiomyocytes, and help regulate vascular tone and cardiac contraction. [1][2][3] In contrast, iNOS is induced in the myocardium in response to various stimuli such as inflammatory mediators, cytokines, and growth factors as well as hypoxia and ischemia, 4,5 and its expression correlates positively with the severity of cardiac dysfunction and cytokine expression. 6,7 Induction and/or activation of iNOS will produce larger amounts of NO, which reacts with superoxide (O 2 Ϫ ) to form the highly cytotoxic oxidant peroxynitrite (ONOO Ϫ ). Recently, it has been demonstrated that iNOS is also capable of producing O 2 Ϫ , which is transformed to hydrogen peroxide (H 2 O 2 ) either spontaneously or via an enzymatic reaction with superoxide dismutase. 8,9 Both ONOO Ϫ and H 2 O 2 have been implicated in tissue injury and organ dysfunction, including the heart. 10 -12 The role of iNOS in the pathophysiology of hypertension and cardiac hypertrophy remains controversial. A number of studies have shown that iNOS expression and activity are altered in hypertens...

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Section: Sun Et Al Role Of Inos In Doca-salt Hypertension 1359mentioning

confidence: 71%

Lack of Inducible NO Synthase Reduces Oxidative Stress and Enhances Cardiac Response to Isoproterenol in Mice With Deoxycorticosterone Acetate–Salt Hypertension

et al. 2005

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“…This study also reported that whole cell LVA currents could only be observed in half of the cells. In contrast, LVA currents were never detected in freshly isolated coronary SMCs from rabbits (269) or humans (332). LVA currents were found if the cells were cultured, and these currents appear to be T type based on their voltage dependence and 1:1 conductance of Ca 2ϩ and Ba 2ϩ (332).…”

Section: E Smooth Musclementioning

confidence: 99%

“…LVA currents have been found in the following arterial SMCs: coronary (130,281,332), aortic (3), mesenteric (150,311,372), rabbit ear (34), rat tail (327,428), and middle cerebral arterioles (167). RT-PCR detected the expression of both Ca v 3.1 and Ca v 3.2 in rat mesenteric arterioles (150).…”

Section: E Smooth Musclementioning

confidence: 99%

“…In contrast, LVA currents were never detected in freshly isolated coronary SMCs from rabbits (269) or humans (332). LVA currents were found if the cells were cultured, and these currents appear to be T type based on their voltage dependence and 1:1 conductance of Ca 2ϩ and Ba 2ϩ (332). Similar results have been obtained with aortic SMCs; T-type currents are expressed in proliferating cultures, but neither in confluent cultures (3,339) nor in freshly isolated cells (220).…”

Section: E Smooth Musclementioning

confidence: 99%

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Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels

Perez‐Reyes

2003

Physiological Reviews

1,501

1,446

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T-type Ca2+ channels were originally called low-voltage-activated (LVA) channels because they can be activated by small depolarizations of the plasma membrane. In many neurons Ca2+ influx through LVA channels triggers low-threshold spikes, which in turn triggers a burst of action potentials mediated by Na+ channels. Burst firing is thought to play an important role in the synchronized activity of the thalamus observed in absence epilepsy, but may also underlie a wider range of thalamocortical dysrhythmias. In addition to a pacemaker role, Ca2+ entry via T-type channels can directly regulate intracellular Ca2+ concentrations, which is an important second messenger for a variety of cellular processes. Molecular cloning revealed the existence of three T-type channel genes. The deduced amino acid sequence shows a similar four-repeat structure to that found in high-voltage-activated (HVA) Ca2+ channels, and Na+ channels, indicating that they are evolutionarily related. Hence, the α1-subunits of T-type channels are now designated Cav3. Although mRNAs for all three Cav3 subtypes are expressed in brain, they vary in terms of their peripheral expression, with Cav3.2 showing the widest expression. The electrophysiological activities of recombinant Cav3 channels are very similar to native T-type currents and can be differentiated from HVA channels by their activation at lower voltages, faster inactivation, slower deactivation, and smaller conductance of Ba2+. The Cav3 subtypes can be differentiated by their kinetics and sensitivity to block by Ni2+. The goal of this review is to provide a comprehensive description of T-type currents, their distribution, regulation, pharmacology, and cloning.

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“…This pathway is activated by NO and leads to the formation of cGMP. L-type Ca 2 þ channel activity is inhibited by cGMP/cGMP-dependent protein kinase (PKG) stimulation in a wide variety of smooth muscles (canine colon, Koh & Sanders, 1996; human coronary artery, Quignard et al, 1997;rabbit portal vein, Ruiz-Velasco et al, 1998). This is thought to result from PKG causing the phosphorylation of an inhibitory binding site associated with L-type Ca 2 þ channels (Ruiz-Velasco et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Modulation of voltage‐dependent Ba²⁺ currents in the guinea‐pig gastric antrum by cyclic nucleotide‐dependent pathways

Zhu

Hirst

Ito

et al. 2005

British J Pharmacology

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1 We have investigated whether the activation of cAMP-and cGMP-dependent pathways modifies the properties of voltage-dependent Ba 2 þ currents (I Ba ) recorded from guinea-pig gastric myocytes using patch-clamp techniques. All experiments were carried on single smooth muscle cells, dispersed from the circular layer of the guinea-pig gastric antrum. 2 Both dibutyryl cAMP (db-cAMP, 0.1-1 mM), a membrane-permeable ester of cAMP, and isoproterenol, a selective b-stimulant, inhibited I Ba in a concentration-dependent manner. 3 Forskolin, but not dideoxy-forskolin, an inactive isomer of forskolin, inhibited the peak amplitude of I Ba . 4 In the presence of either Rp-cAMP or the PKA (cAMP-dependent protein kinase) inhibitor peptide 5-24 (PKA-IP), neither forskolin nor db-cAMP inhibited I Ba . 5 After establishing a conventional whole-cell recording, the peak amplitude of I Ba gradually decreased when the catalytic subunit of PKA was included in the pipette. The further application of Rp-cAMP reversibly enhanced I Ba . 6 Sodium nitroprusside (0.1-1 mM) and 8-Br-cGMP (0.1-1 mM) also inhibited I Ba in a concentrationdependent manner. 7 The inhibitory effects of forskolin or db-cAMP on I Ba were not significantly changed by pretreatment with a cGMP-dependent protein kinase (PKG) inhibitor. Similarly, the inhibitory actions of 8-Br-cGMP on I Ba were not modified by PKA-IP. 8 The membrane-permeable cyclic nucleotides db-cAMP and 8-Br-cGMP caused little shift of the voltage dependence of the steady-state inactivation and reactivation curves. 9 Neither of the membrane-permeable cyclic nucleotides db-cAMP or 8-Br-cGMP had additive inhibitory effects on I Ba . 10 These results indicate that two distinct cyclic nucleotide-dependent pathways are present in the guinea-pig gastric antrum, and that both inhibited I Ba in an independent manner.

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Voltage-gated calcium channel currents in human coronary myocytes. Regulation by cyclic GMP and nitric oxide.

Cited by 78 publications

References 45 publications

Lack of Inducible NO Synthase Reduces Oxidative Stress and Enhances Cardiac Response to Isoproterenol in Mice With Deoxycorticosterone Acetate–Salt Hypertension

Lack of Inducible NO Synthase Reduces Oxidative Stress and Enhances Cardiac Response to Isoproterenol in Mice With Deoxycorticosterone Acetate–Salt Hypertension

Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels

Modulation of voltage‐dependent Ba²⁺ currents in the guinea‐pig gastric antrum by cyclic nucleotide‐dependent pathways

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Voltage-gated calcium channel currents in human coronary myocytes. Regulation by cyclic GMP and nitric oxide.

Cited by 78 publications

References 45 publications

Lack of Inducible NO Synthase Reduces Oxidative Stress and Enhances Cardiac Response to Isoproterenol in Mice With Deoxycorticosterone Acetate–Salt Hypertension

Lack of Inducible NO Synthase Reduces Oxidative Stress and Enhances Cardiac Response to Isoproterenol in Mice With Deoxycorticosterone Acetate–Salt Hypertension

Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels

Modulation of voltage‐dependent Ba2+ currents in the guinea‐pig gastric antrum by cyclic nucleotide‐dependent pathways

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Modulation of voltage‐dependent Ba²⁺ currents in the guinea‐pig gastric antrum by cyclic nucleotide‐dependent pathways