Mibefradil and Flunarizine, Two T-Type Calcium Channel Inhibitors, Protect Mice against Lipopolysaccharide-Induced Acute Lung Injury

Wan, Limei; Wu, Weibin; Jiang, Shunjun; Wan, Shanhe; Meng, Dong; Wang, Zhipeng; Zhang, Jiajie; Li, Wei; Yu, P.Y.

doi:10.1155/2020/3691701

Cited by 8 publications

(3 citation statements)

References 48 publications

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“…6 B; P <0.01 for pimozide+ZD versus pimozide, unpaired t -test). Additionally, adding T-type Ca 2+ channel blocker mibefradil (Mib; 10 µM) ( Wan et al, 2020 ) into perfusion solution occluded the facilitation effect of ZD7288 on mIPSC frequency ( P >0.05), while perfusing Mib (10 µM) alone had no impact on the frequency of mIPSC ( P >0.05). But facilitation of ZD7288 on mIPSC frequency still exists in the presence of the P/Q-type Ca 2+ channel blocker ω-agatoxin IVA (500 nM), the N-type Ca 2+ channel blocker ω-conotoxin GVIA (500 nM), and the L-type Ca 2+ channel blocker nifedipine ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Presynaptic HCN channels constrain GABAergic synaptic transmission in pyramidal cells of the medial prefrontal cortex

Cai

Liu

et al. 2022

Biology Open

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Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are widely expressed in neurons in the central nervous system. It has been documented that HCN channels regulate the intrinsic excitability of pyramidal cells in the medial prefrontal cortex (mPFC) of rodents. Here, we report that HCN channels limited GABAergic transmission onto pyramidal cells in rat mPFC. The pharmacological blockade of HCN channels resulted in a significant increase in the frequency of both spontaneous and miniature inhibitory postsynaptic currents (IPSCs) in mPFC pyramidal cells, whereas potentiation of HCN channels reversely decreases the frequency of mIPSCs. Furthermore, such facilitation effect on mIPSC frequency required presynaptic Ca2+ influx. Immunofluorescence staining showed that HCN channels expressed in presynaptic GABAergic terminals, as well as in both soma and neurite of parvalbumin-expressing (PV-expressing) basket cells in mPFC. The present results indicate that HCN channels in GABAergic interneurons, most likely PV-expressing basket cells, constrain inhibitory control over layer 5-6 pyramidal cells by restricting presynaptic Ca2+ entry.

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Section: Resultsmentioning

confidence: 99%

Presynaptic HCN channels constrain GABAergic synaptic transmission in pyramidal cells of the medial prefrontal cortex

Cai

Liu

et al. 2022

Biology Open

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“…6B; p <0.01 for pimozide+ZD vs. pimozide, unpaired t -test). Additionally, Adding T-type Ca2+ channel blocker mibefradil (Mib; 10 μM)[44] into perfusion solution occluded the facilitation effect of ZD7288 on mIPSC frequency (p>0.05), while perfusing Mib (10 μM) alone did not affect the frequency of mIPSC (p>0.05). But the facilitation of ZD7288 on mIPSC frequency still exist in the presence of the P/Q-type Ca 2+ channel blocker ω-agatoxin IVA (500 nM), the N-type Ca 2+ channel blocker ω-conotoxin GVIA (500 nM), and the L-type Ca 2+ channel blocker nifedipine (Fig.…”

Section: Resultsmentioning

confidence: 99%

Presynaptic HCN channels constrain GABAergic synaptic transmission in pyramidal cells of the medial prefrontal cortex

Cai

Liu

et al. 2021

Preprint

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Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are widely expressed in neurons in the central nervous system. It has been documented that HCN channels regulate the intrinsic excitability of pyramidal cells in the medial prefrontal cortex (mPFC) of rats. Here, we report that HCN channels limited GABAergic transmission onto pyramidal cells in the mPFC. Pharmacological block of HCN channels resulted in a significant increase in the frequency of both spontaneous and miniature inhibitory postsynaptic currents (IPSCs) in mPFC pyramidal cells. Such facilitation effect on mIPSCs required presynaptic Ca2+ influx and reversed by high-dose cAMP. Such facilitation did not exist in the presence of the T-type Ca2+ channel selective blockers. Immunofluorescence staining revealed that HCN channels expressed in presynaptic GABAergic terminals, as well as in both soma and neurite of parvalbumin-expressing (PV-expressing) basket cells in the mPFC. The present results indicate that HCN channels in GABAergic interneurons, most likely PV-expressing basket cells, constrain inhibitory control over layer 5-6 pyramidal cells through restricting presynaptic Ca2+ entry.

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“…Interestingly, there is indirect evidence linking IL-6 and T-channels. T-type inhibitors ameliorate the effects of inflammatory processes related to IL-6 [58,59], and IL-6 regulates T-type channels expression and function [60][61][62].…”

Section: Limitationsmentioning

confidence: 99%

Secretion of Interleukin 6 in Human Skeletal Muscle Cultures Depends on Ca2+ Signalling

Calle-Ciborro,

Espin-Jaime,

Santos

et al. 2023

Biology

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The systemic effects of physical activity are mediated by the release of IL-6 and other myokines from contracting muscle. Although the release of IL-6 from muscle has been extensively studied, the information on the cellular mechanisms is fragmentary and scarce, especially regarding the role of Ca2+ signals. The aim of this study was to characterize the role of the main components of Ca2+ signals in human skeletal muscle cells during IL-6 secretion stimulated by the Ca2+ mobilizing agonist ATP. Primary cultures were prepared from surgical samples, fluorescence microscopy was used to evaluate the Ca2+ signals and the stimulated release of IL-6 into the medium was determined using ELISA. Intracellular calcium chelator Bapta, low extracellular calcium and the Ca2+ channels blocker La3+ reduced the ATP-stimulated, but not the basal secretion. Secretion was inhibited by blockers of L-type (nifedipine, verapamil), T-type (NNC55-0396) and Orai1 (Synta66) Ca2+ channels and by silencing Orai1 expression. The same effect was achieved with inhibitors of ryanodine receptors (ryanodine, dantrolene) and IP3 receptors (xestospongin C, 2-APB, caffeine). Inhibitors of calmodulin (calmidazolium) and calcineurin (FK506) also decreased secretion. IL-6 transcription in response to ATP was not affected by Bapta or by the T channel blocker. Our results prove that ATP-stimulated IL-6 secretion is mediated at the post-transcriptional level by Ca2+ signals, including the mobilization of calcium stores, the activation of store-operated Ca2+ entry, and the subsequent activation of voltage-operated Ca2+ channels and calmodulin/calcineurin pathways.

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Mibefradil and Flunarizine, Two T-Type Calcium Channel Inhibitors, Protect Mice against Lipopolysaccharide-Induced Acute Lung Injury

Cited by 8 publications

References 48 publications

Presynaptic HCN channels constrain GABAergic synaptic transmission in pyramidal cells of the medial prefrontal cortex

Presynaptic HCN channels constrain GABAergic synaptic transmission in pyramidal cells of the medial prefrontal cortex

Presynaptic HCN channels constrain GABAergic synaptic transmission in pyramidal cells of the medial prefrontal cortex

Secretion of Interleukin 6 in Human Skeletal Muscle Cultures Depends on Ca2+ Signalling

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