CaV3.2 T-type Ca2+ channels in H2S-mediated hypoxic response of the carotid body

Makarenko, Vladislav; Peng, Ying; Yuan, Guoxiang; Fox, Aaron P.; Kumar, Ganesh K.; Nanduri, Jayasri; Prabhakar, Nanduri R.

doi:10.1152/ajpcell.00141.2014

Cited by 18 publications

(23 citation statements)

References 32 publications

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“…Hypoxia induces Ca 2+ -dependent release of catecholamines (CAs) in glomus cells of the carotid body, an organ sensing arterial blood O 2 concentration, which is essential for controlling the function of respiratory and cardiovascular systems [22] . The hypoxia-induced secretion of CAs is observed also in the adrenal medullary chromaffin cells [52] .…”

Section: Involvement Of the H 2 S/ca V 32 Pathway In The Hypoxia-indmentioning

confidence: 99%

Hydrogen Sulfide and T-Type Ca2+ Channels in Pain Processing, Neuronal Differentiation and Neuroendocrine Secretion

Fukami

Sekiguchi²,

Kawabata³

2016

Pharmacology

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Background: Hydrogen sulfide (H₂S), a gasotransmitter, is generated from L-cysteine by mainly 3 enzymes, cystathionine-γ-lyase (CSE), cystathionine-β-synthase, and 3-mercaptopyruvate sulfurtransferase in cooperation with cysteine aminotransferase. The H₂S-forming enzymes, particularly CSE, are overexpressed under the pathological conditions such as inflammation, neuronal or neuroendocrine differentiation and cancer development. Given that Ca_v3.2 T-type Ca²⁺ channels mediate some of the biological activity of H₂S, we focus on the role of the H₂S/Ca_v3.2 pathway in regulating the neuronal and neuroendocrine function. Summary: In the neuronal system, H₂S regulates the activity of various ion channels including Ca_v3.2. Exogenous and endogenous H₂S enhances the Ca_v3.2 channel activity, promoting somatic and visceral pain signaling. The H₂S/Ca_v3.2 pathway also facilitates neuritogenesis or neuronal differentiation. Interestingly, endogenous H₂S formed by CSE regulates secretory function by enhancing Ca_v3.2 channel activity in neuroendocrine-differentiated prostate cancer cells or carotid glomus cells. Key Messages: The H₂S/Ca_v3.2 pathway may serve as therapeutic targets for treatment of intractable pain, neuronal injury, androgen-independent prostate cancer, cardiovascular diseases, etc.

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Section: Involvement Of the H 2 S/ca V 32 Pathway In The Hypoxia-indmentioning

confidence: 99%

Hydrogen Sulfide and T-Type Ca2+ Channels in Pain Processing, Neuronal Differentiation and Neuroendocrine Secretion

Fukami

Sekiguchi²,

Kawabata³

2016

Pharmacology

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“…However, people living at sea level most often experience intermittent hypoxia (IH) as a consequence of sleep apnea (i.e., brief, repetitive cessation of breathing) (22). IH, mimicking O 2 profiles encountered during sleep apnea, affects various cellular functions including activation of early genes (31), hypoxia-inducible factor (HIF)-1␣ (33), and voltage-gated Ca 2ϩ channels (14). Sleep apnea patients and IH-exposed rodents exhibit cardiovascular abnormalities, including hypertension and cardiac arrhythmias (18,30).…”

mentioning

confidence: 99%

Calpain activation by ROS mediates human ether-a-go-go-related gene protein degradation by intermittent hypoxia

Wang

Kang

Ahmmed

et al. 2016

American Journal of Physiology-Cell Physiology

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man ether-a-go-go-related gene (hERG) channels conduct delayed rectifier K ϩ current. However, little information is available on physiological situations affecting hERG channel protein and function. In the present study we examined the effects of intermittent hypoxia (IH), which is a hallmark manifestation of sleep apnea, on hERG channel protein and function. Experiments were performed on SH-SY5Y neuroblastoma cells, which express hERG protein. Cells were exposed to IH consisting of alternating cycles of 30 s of hypoxia (1.5% O2) and 5 min of 20% O2. IH decreased hERG protein expression in a stimulus-dependent manner. A similar reduction in hERG protein was also seen in adrenal medullary chromaffin cells from IH-exposed neonatal rats. The decreased hERG protein was associated with attenuated hERG K ϩ current. IH-evoked hERG protein degradation was not due to reduced transcription or increased proteosome/lysomal degradation. Rather it was mediated by calciumactivated calpain proteases. Both COOH-and NH2-terminal sequences of the hERG protein were the targets of calpain-dependent degradation. IH increased reactive oxygen species (ROS) levels, intracellular Ca 2ϩ concentration ([Ca 2ϩ ]i), calpain enzyme activity, and hERG protein degradation, and all these effects were prevented by manganese-(111)-tetrakis-(1-methyl-4-pyridyl)-porphyrin pentachloride, a membrane-permeable ROS scavenger. These results demonstrate that activation of calpains by ROS-dependent elevation of [Ca 2ϩ ]i mediates hERG protein degradation by IH. sleep apnea; oxidative stress; arrhythmia; apnea of prematurity; adrenal medullary chromaffin cells

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“…The protocols for recording sensory nerve activity from ex vivo carotid bodies from mice were essentially the same as described previously (Makarenko et al 2015). Briefly, the carotid body with the sinus nerve was placed in a recording chamber (250 l vol) and superfused at a rate of 2.5 ml/min with warm (36°C) physiological saline (in mM: 125 NaCl, 5 KCl, 1.8 CaCl 2 , 2 MgSO 4 , 1.2 NaH 2 PO 4 , 25 NaHCO 3 , 10 D-glucose, and 5 sucrose).…”

Section: Methodsmentioning

confidence: 99%

“…We recently reported that low-threshold T-type VGCC, especially the CaV3.2, plays an equally important role in mediating hypoxia-induced Ca 2ϩ influx in glomus cells (Makarenko et al 2015). In the present study, we examined the effects of CIH on the glomus cell [Ca 2ϩ ] i response to hypoxia and assessed the role of VGCC.…”

mentioning

confidence: 89%

“…Nifedipine, by itself, inhibited the [Ca 2ϩ ] i response in CIHtreated glomus cells by 40 Ϯ 4%, as opposed to 60 Ϯ 8.5% inhibition in control glomus cells (P Ͻ 0.05), suggesting that nifedipine was less effective in blocking the augmented [Ca 2ϩ ] i response by CIH compared with TTA-A2. CaV3.2 is the primary T-type VGCC expressed in glomus cells (Makarenko et al 2015). To assess the selective contri- Ϫ/Ϫ mice.…”

Section: Effect Of Cih On Reactive Oxygen Species (Ros) Levels In Rmentioning

confidence: 99%

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CaV3.2 T-type Ca²⁺channels mediate the augmented calcium influx in carotid body glomus cells by chronic intermittent hypoxia

Makarenko

Ahmmed

Peng

et al. 2016

Journal of Neurophysiology

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] i ) in glomus cells, the primary oxygensensing cells, is an essential step for carotid body activation by hypoxia. In the present study, we examined the effects of CIH on the glomus cell [Ca 2ϩ ] i response to hypoxia and assessed the underlying mechanisms. Glomus cells were harvested from adult rats or wild-type mice treated with 10 days of either room air (control) or CIH (alternating cycles of 15 s of hypoxia and 5 min of room air; 9 episodes/h; 8 h/day). CIH-treated glomus cells exhibited an enhanced [Ca 2ϩ ] i response to hypoxia, and this effect was absent in the presence of 2-(4-cyclopropylphenyl)-N-((1R)-1-[5-[(2,2,2-trifluoroethyl)oxo]-pyridin-2-yl]ethyl)acetamide (TTA-A2), a specific inhibitor of T-type Ca 2ϩ channels, and in voltage-gated calcium channel, type 3.2 (CaV3.2), null glomus cells. CaV3.2 knockout mice exhibited an absence of CIH-induced hypersensitivity of the carotid body. CIH increased reactive oxygen species (ROS) levels in glomus cells. A ROS scavenger prevented the exaggerated TTA-A2-sensitive [Ca 2ϩ ] i response to hypoxia. CIH had no effect on CaV3.2 mRNA levels. CIH augmented Ca 2ϩ currents and increased CaV3.2 protein in plasma membrane fractions of human embryonic kidney-293 cells stably expressing CaV3.2, and either a ROS scavenger or brefeldin-A, an inhibitor of protein trafficking, prevented these effects. These findings suggest that CIH leads to an augmented Ca 2ϩ influx via ROSdependent facilitation of CaV3.2 protein trafficking to the plasma membrane. sleep apnea; voltage-gated Ca 2ϩ channels; hypertension; protein trafficking; oxidative stress SLEEP-DISORDERED BREATHING with recurrent apnea is a major clinical problem affecting an estimated 9% of adult women and 24% of adult men in the United States (Young et al.

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Ca_V3.2 T-type Ca²⁺ channels in H₂S-mediated hypoxic response of the carotid body

Cited by 18 publications

References 32 publications

Hydrogen Sulfide and T-Type Ca<sup>2+</sup> Channels in Pain Processing, Neuronal Differentiation and Neuroendocrine Secretion

Hydrogen Sulfide and T-Type Ca<sup>2+</sup> Channels in Pain Processing, Neuronal Differentiation and Neuroendocrine Secretion

Calpain activation by ROS mediates human ether-a-go-go-related gene protein degradation by intermittent hypoxia

CaV3.2 T-type Ca²⁺channels mediate the augmented calcium influx in carotid body glomus cells by chronic intermittent hypoxia

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CaV3.2 T-type Ca2+ channels in H2S-mediated hypoxic response of the carotid body

Cited by 18 publications

References 32 publications

Hydrogen Sulfide and T-Type Ca<sup>2+</sup> Channels in Pain Processing, Neuronal Differentiation and Neuroendocrine Secretion

Hydrogen Sulfide and T-Type Ca<sup>2+</sup> Channels in Pain Processing, Neuronal Differentiation and Neuroendocrine Secretion

Calpain activation by ROS mediates human ether-a-go-go-related gene protein degradation by intermittent hypoxia

CaV3.2 T-type Ca2+channels mediate the augmented calcium influx in carotid body glomus cells by chronic intermittent hypoxia

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Ca_V3.2 T-type Ca²⁺ channels in H₂S-mediated hypoxic response of the carotid body

CaV3.2 T-type Ca²⁺channels mediate the augmented calcium influx in carotid body glomus cells by chronic intermittent hypoxia