Blockade by NNC 55-0396, mibefradil, and nickel of calcium and exocytotic signals in chromaffin cells: Implications for the regulation of hypoxia-induced secretion at early life

Fernández-Morales, José Carlos; Padín, Juan Fernando; Vestring, Stefan; Musial, Diego Castro; Diego, Antonio M. G. de; Garcı́a, Antonio G.

doi:10.1016/j.ejphar.2015.01.025

Cited by 2 publications

(1 citation statement)

References 36 publications

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“…Actually, [Ca 2+ ] i responses to 15K were inhibited by several T‐type Ca 2+ channel blockers in mouse DRG neurons. It has been reported that these blockers, especially NNC 55‐0396, are adequate pharmacological tool to discern the contribution of T‐type Ca 2+ channels (Fernández‐Morales et al, ). Although in the present experiment the inhibitory potency of TTA‐A2 was somewhat low (Kraus et al, ), a similar range of concentration (25 µM) has been used to suppress T‐type Ca 2+ channel‐dependent [Ca 2+ ] i responses to hypoxia in glomus cells of rat carotid body (Makarenko et al, ).…”

Section: Discussionmentioning

confidence: 99%

Possible involvement of transient receptor potential ankyrin 1 in Ca²⁺ signaling via T‐type Ca²⁺ channel in mouse sensory neurons

Nishizawa

Takahashi

Oguma

et al. 2017

J of Neuroscience Research

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T-type Ca channels and TRPA1 are expressed in sensory neurons and both are associated with pain transmission, but their functional interaction is unclear. Here we demonstrate that pharmacological evidence of the functional relation between T-type Ca channels and TRPA1 in mouse sensory neurons. Low concentration of KCl at 15 mM (15K) evoked increases of intracellular Ca concentration ([Ca ] ), which were suppressed by selective T-type Ca channel blockers. RT-PCR showed that mouse sensory neurons expressed all subtypes of T-type Ca channel. The magnitude of 15K-induced [Ca ] increase was significantly larger in neurons sensitive to allylisothiocyanate (AITC, a TRPA1 agonist) than in those insensitive to it, and in TRPA1 mouse sensory neurons. TRPA1 blockers diminished the [Ca ] responses to 15K in neurons sensitive to AITC, but failed to inhibit 40 mM KCl-induced [Ca ] increases even in AITC-sensitive neurons. TRPV1 blockers did not inhibit the 15K-induced [Ca ] increase regardless of the sensitivity to capsaicin. [Ca ] responses to TRPA1 agonist were enhanced by co-application with 15K. These pharmacological data suggest the possibility of functional interaction between T-type Ca channels and TRPA1 in sensory neurons. Since TRPA1 channel is activated by intracellular Ca , we hypothesize that Ca entered via T-type Ca channel activation may further stimulate TRPA1, resulting in an enhancement of nociceptive signaling. Thus, T-type Ca channel may be a potential target for TRPA1-related pain.

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Section: Discussionmentioning

confidence: 99%

Possible involvement of transient receptor potential ankyrin 1 in Ca²⁺ signaling via T‐type Ca²⁺ channel in mouse sensory neurons

Nishizawa

Takahashi

Oguma

et al. 2017

J of Neuroscience Research

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Oxygen sensor of the heart

Fernández‐Morales¹,

Morad

2022

Can. J. Physiol. Pharmacol.

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How oxygen is sensed by the heart and what mechanisms mediate its sensing remain poorly understood. As recent reports show that low PO2 levels are detected by the cardiomyocytes in a few seconds, the rapid and short applications of low levels of oxygen (acute hypoxia), which avoid multiple effects of chronic hypoxia, may be used to probe the oxygen-sensing pathway of the heart. Here, we explored the oxygen-sensing pathway, focusing primarily on cellular surface membrane proteins that were first exposed to low PO2. Such studies suggest that acute hypoxia primarily targets the cardiac calcium channels, where either the channel itself or moieties closely associated with it, for instance heme-oxygenase-2 (HO-2) interacting through kinase phosphorylation, signal the α-subunit of the channel to the altered levels of PO2. Amino acids 1572–1651, the CaMKII phosphorylation sites (S1487 and S1545), CaM-binding sites (I1624 and Q1625), and Ser1928 of the carboxyl tail of the α-subunit appear to be critical residues that sense oxygen. Future studies on HO-2 knockout mice or CRISPR/Cas9 gene-edited human-induced pluripotent stem-cell-derived cardiomyocytes that reduce CaM-binding affinity are likely to provide deeper insights into the O2-sensing mechanisms.

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Blockade by NNC 55-0396, mibefradil, and nickel of calcium and exocytotic signals in chromaffin cells: Implications for the regulation of hypoxia-induced secretion at early life

Cited by 2 publications

References 36 publications

Possible involvement of transient receptor potential ankyrin 1 in Ca²⁺ signaling via T‐type Ca²⁺ channel in mouse sensory neurons

Possible involvement of transient receptor potential ankyrin 1 in Ca²⁺ signaling via T‐type Ca²⁺ channel in mouse sensory neurons

Oxygen sensor of the heart

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Blockade by NNC 55-0396, mibefradil, and nickel of calcium and exocytotic signals in chromaffin cells: Implications for the regulation of hypoxia-induced secretion at early life

Cited by 2 publications

References 36 publications

Possible involvement of transient receptor potential ankyrin 1 in Ca2+ signaling via T‐type Ca2+ channel in mouse sensory neurons

Possible involvement of transient receptor potential ankyrin 1 in Ca2+ signaling via T‐type Ca2+ channel in mouse sensory neurons

Oxygen sensor of the heart

Contact Info

Product

Resources

About

Possible involvement of transient receptor potential ankyrin 1 in Ca²⁺ signaling via T‐type Ca²⁺ channel in mouse sensory neurons

Possible involvement of transient receptor potential ankyrin 1 in Ca²⁺ signaling via T‐type Ca²⁺ channel in mouse sensory neurons