Hydrogen Sulfide Raises Cytosolic Calcium in Neurons Through Activation of L-Type Ca<sup>2+</sup> Channels

García-Bereguiaín, Miguel Angel; Samhan-Arias, Alejandro K.; Martı́n-Romero, Francisco Javier; Gutiérrez‐Merino, Carlos

doi:10.1089/ars.2007.1656

Cited by 117 publications

(100 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This indicates that H 2 S promotes neuronal ACh release in a Ca 2ϩ -dependent manner. Similarly, previous studies have demonstrated that H 2 S raises ACh release in a Ca 2ϩ -dependent manner in type I glomus cells (31), in neurons (12,52), astrocytes (33), and microglia (29).…”

Section: Discussionsupporting

confidence: 71%

See 1 more Smart Citation

Novel mechanism of hydrogen sulfide-induced guinea pig urinary bladder smooth muscle contraction: role of BK channels and cholinergic neurotransmission

Fernandes

Xin

Petkov

2015

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

Fernandes VS, Xin W, Petkov GV. Novel mechanism of hydrogen sulfide-induced guinea pig urinary bladder smooth muscle contraction: role of BK channels and cholinergic neurotransmission. Am J Physiol Cell Physiol 309: C107-C116, 2015. First published May 6, 2015; doi:10.1152/ajpcell.00021.2015.-Hydrogen sulfide (H2S) is a key signaling molecule regulating important physiological processes, including smooth muscle function. However, the mechanisms underlying H2S-induced detrusor smooth muscle (DSM) contractions are not well understood. This study investigates the cellular and tissue mechanisms by which H2S regulates DSM contractility, excitatory neurotransmission, and large-conductance voltage-and Ca 2ϩ -activated K ϩ (BK) channels in freshly isolated guinea pig DSM. We used a multidisciplinary experimental approach including isometric DSM tension recordings, colorimetric ACh measurement, Ca 2ϩ imaging, and patch-clamp electrophysiology. In isolated DSM strips, the novel slow release H2S donor, P-(4-methoxyphenyl)-p-4-morpholinylphosphinodithioic acid morpholine salt (GYY4137), significantly increased the spontaneous phasic and nerve-evoked DSM contractions. The blockade of neuronal voltage-gated Na ϩ channels or muscarinic ACh receptors with tetrodotoxin or atropine, respectively, reduced the stimulatory effect of GYY4137 on DSM contractility. GYY4137 increased ACh release from bladder nerves, which was inhibited upon blockade of L-type voltage-gated Ca 2ϩ channels with nifedipine. Furthermore, GYY4137 increased the amplitude of the Ca 2ϩ transients and basal Ca 2ϩ levels in isolated DSM strips. GYY4137 reduced the DSM relaxation induced by the BK channel opener, NS11021. In freshly isolated DSM cells, GYY4137 decreased the amplitude and frequency of transient BK currents recorded in a perforated whole cell configuration and reduced the single BK channel open probability measured in excised inside-out patches. GYY4137 inhibited spontaneous transient hyperpolarizations and depolarized the DSM cell membrane potential. Our results reveal the novel findings that H2S increases spontaneous phasic and nerveevoked DSM contractions by activating ACh release from bladder nerves in combination with a direct inhibition of DSM BK channels. detrusor smooth muscle; GYY4137; acetylcholine; Ca 2ϩ transients DETRUSOR SMOOTH MUSCLE (DSM) is the major component of the urinary bladder wall. Coordinated complex mechanisms involving the contraction and relaxation of DSM facilitate bladder voiding and filling phases (1). DSM contractions in rodents are induced by two main neurotransmitters, ACh and ATP, which are released from parasympathetic nerve endings (1). However, in humans, evidence points to ACh as the major neurotransmitter triggering DSM voiding contractions (7, 34).In experimental animals and humans, activation of muscarinic ACh receptors (mAChRs) depolarizes the DSM cell membrane potential, enhances action potential generation, promotes influx of Ca 2ϩ via L-type voltage-gated Ca 2ϩ (Ca V ) channels, and leads to increased D...

show abstract

Section: Discussionsupporting

confidence: 71%

“…It has been suggested that H 2 S regulates Ca 2ϩ homeostasis in neuronal cells via activation of L-type Ca V channels, and thereby regulates the neurotransmitter release (12,27,52). In the central nervous system, H 2 S promotes synaptic release of glutamate (3).…”

mentioning

confidence: 99%

Novel mechanism of hydrogen sulfide-induced guinea pig urinary bladder smooth muscle contraction: role of BK channels and cholinergic neurotransmission

Fernandes

Xin

Petkov

2015

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

show abstract

“…While short application (Ͻ15 min) of relatively low concentration of NaHS (Յ130 M) did not induce any current via NMDA receptor (20), overnight incubation with higher concentration of NaHS (200 -1000 M) alone caused neuronal death that is totally preventable by pretreatment with NMDAR antagonists (9). Our results may be in line with the latter study since we incubated primary cortical neurons with H 2 S donors for 24 h. On the other hand, H 2 S may activate other calcium channels and thereby indirectly activate NMDA receptors via releasing glutamate (21). Taken together, these observations support the hypothesis that cytotoxicity of H 2 S is at least in part mediated via enhancement of NMDAR activation.…”

Section: Discussionsupporting

confidence: 87%

A Novel Hydrogen Sulfide-releasing N-Methyl-d-Aspartate Receptor Antagonist Prevents Ischemic Neuronal Death

Marutani

Kosugi

Tokuda

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:Hydrogen sulfide (H 2 S) exerts neuroprotective effects, whereas H 2 S may cause neurotoxicity via N-methyl-D-aspartate receptor (NMDAR) activation. Results: A newly-synthesized H 2 S-releasing NMDAR antagonist S-memantine exerted lower neurotoxicity and prevented ischemic neuronal death more markedly than conventional H 2 S-releasing compounds or memantine alone. Conclusion: S-memantine prevents ischemic brain injury without neurotoxicity. Significance: H 2 S-releasing NMDAR antagonists may prevent neurodegeneration of various causes.

show abstract

“…This increased discharge is likely due to elevated levels of intracellular cytosolic calcium. It is well known that activity-dependent intracellular calcium overload may result in neuronal apoptosis (4,16,23). Thus, the possibility exists that one of the main functions of STC-1 within SFO is to reduce the influx and the rise in intracellular calcium levels (10, 70).…”

Section: Perspectives and Significancementioning

confidence: 99%

Stanniocalcin-1 in the subfornical organ inhibits the dipsogenic response to angiotensin II

Moreau

Iqbal

Turner

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

in the subfornical organ inhibits the dipsogenic response to angiotensin II. Am J Physiol Regul Integr Comp Physiol 303: R921-R928, 2012. First published August 29, 2012 doi:10.1152 doi:10. /ajpregu.00057.2012 for the calcium-regulating glycoprotein hormone stanniocalcin-1 (STC-1) have been found within subfornical organ (SFO), a central structure involved in the regulation of electrolyte and body fluid homeostasis. However, whether SFO neurons produce STC-1 and how STC-1 may function in fluid homeostasis are not known. Two series of experiments were done in Sprague-Dawley rats to investigate whether STC-1 is expressed within SFO and whether it exerts an effect on water intake. In the first series, experiments were done to determine whether STC-1 was expressed within cells in SFO using immunohistochemistry, and whether protein and gene expression for STC-1 existed in SFO using Western blot and quantitative RT-PCR, respectively. Cells containing STC-1 immunoreactivity were found throughout the rostrocaudal extent of SFO. STC-1 protein expression within SFO was confirmed with Western blot, and SFO was also found to express STC-1 mRNA. In the second series, microinjections (200 nl) of STC-1, ANG II, a combination of the two or the vehicle were made into SFO in conscious, unrestrained rats. Water intake was measured at 0700 for a 1-h period after each injection in animals. Microinjections of STC-1 (17.6 or 176 nM) alone had no effect on water intake compared with controls. However, STC-1 not only attenuated the drinking responses to ANG II for about 30 min, but also decreased the total water intake over the 1-h period. These data suggest that STC-1 within the SFO may act in a paracrine/autocrine manner to modulate the neuronal responses to blood-borne ANG II. These findings also provide the first direct evidence of a physiological role for STC-1 in central regulation of body fluid homeostasis. body fluid homeostasis; thirst; circumventricular organs; calciumregulating glycoprotein STANNIOCALCIN (STC) IS A GLYCOPROTEIN hormone first identified and characterized within bony fish corpuscles of Stannius, endocrine glands derived from renal tubular cells (18,24,29,63,64). These glands are thought to produce and release STC into the circulation in response to rising serum calcium levels (11,18,29,64). The STC then acts on the gills and gut epithelial cells to reduce calcium uptake, while STC within the kidney causes increases in reabsorption of phosphate (11,18,24), a mechanism that likely aids in chelating excess extracellular calcium (18,24). The net effect of these STC actions is the restoration of serum calcium levels (14,18,24,62).A mammalian homolog of STC has been identified that shares a 73% amino acid sequence homology with fish STC (41). Mammalian STC-1 is a disulfide-linked glycoprotein dimer of identical subunits (41), which is expressed in a variety of tissues, including heart, kidney, adipose tissue, skeletal muscle, lung, ovaries (18, 24), and brain (67-69). STC-1 functions in the cells of these tissues ...

show abstract

Hydrogen Sulfide Raises Cytosolic Calcium in Neurons Through Activation of L-Type Ca²⁺ Channels

Cited by 117 publications

References 35 publications

Novel mechanism of hydrogen sulfide-induced guinea pig urinary bladder smooth muscle contraction: role of BK channels and cholinergic neurotransmission

Novel mechanism of hydrogen sulfide-induced guinea pig urinary bladder smooth muscle contraction: role of BK channels and cholinergic neurotransmission

A Novel Hydrogen Sulfide-releasing N-Methyl-d-Aspartate Receptor Antagonist Prevents Ischemic Neuronal Death

Stanniocalcin-1 in the subfornical organ inhibits the dipsogenic response to angiotensin II

Contact Info

Product

Resources

About

Hydrogen Sulfide Raises Cytosolic Calcium in Neurons Through Activation of L-Type Ca2+ Channels

Cited by 117 publications

References 35 publications

Novel mechanism of hydrogen sulfide-induced guinea pig urinary bladder smooth muscle contraction: role of BK channels and cholinergic neurotransmission

Novel mechanism of hydrogen sulfide-induced guinea pig urinary bladder smooth muscle contraction: role of BK channels and cholinergic neurotransmission

A Novel Hydrogen Sulfide-releasing N-Methyl-d-Aspartate Receptor Antagonist Prevents Ischemic Neuronal Death

Stanniocalcin-1 in the subfornical organ inhibits the dipsogenic response to angiotensin II

Contact Info

Product

Resources

About

Hydrogen Sulfide Raises Cytosolic Calcium in Neurons Through Activation of L-Type Ca²⁺ Channels