• Biomolecules & Therapeutics
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• 제32권2호
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• pp.192-204
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• 2024

Generally, odorant molecules are detected by olfactory receptors, which are specialized chemoreceptors expressed in olfactory neurons. Besides odorant molecules, certain volatile molecules can be inhaled through the respiratory tract, often leading to pathophysiological changes in the body. These inhaled molecules mediate cellular signaling through the activation of the Ca²⁺-permeable transient receptor potential (TRP) channels in peripheral tissues. This review provides a comprehensive overview of TRP channels that are involved in the detection and response to volatile molecules, including hazardous substances, anesthetics, plant-derived compounds, and pheromones. The review aims to shed light on the biological mechanisms underlying the sensing of inhaled volatile molecules. Therefore, this review will contribute to a better understanding of the roles of TRP channels in the response to inhaled molecules, providing insights into their implications for human health and disease.

• The Korean Journal of Physiology and Pharmacology
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• 제7권4호
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• pp.223-229
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• 2003

Using phospholipase D1 (PLD1)-overexpressing PC12 (PLD1-PC12) cells, the regulatory roles of PLD1 on ATP-induced currents were investigated. In control and PLD1-PC12 cells, ATP increased PLD activity in an external $Ca^{2+}$ dependent manner. PLD activity stimulated by ATP was substantially larger in PLD1-PC12 cells than in control cells. In whole-cell voltage-clamp mode, ATP induced transient inward and outward currents. The outward currents inhibited by TEA or charybdotoxin were significantly larger in PLD1-PC12 cells than in control cells. The inward currents known as $Ca^{2+}$ permeable nonselective cation currents were also larger in PLD1-PC12 cells than in control cells. However, the difference between the two groups of cells disappeared in $Ca^{2+}$-free external solution, where ATP did not activate PLD. Finally, ATP-induced $^{45}Ca$ uptakes were also larger in PLD1-PC12 cells than in control cells. These results suggest that PLD enhances ATP-induced $Ca^{2+}$ influx via $Ca^{2+}$ permeable nonselective cation channels and increases subsequent $Ca^{2+}$-activated $K^+$ currents in PC12 cells.

• The Korean Journal of Physiology and Pharmacology
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• 제21권3호
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• pp.327-334
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• 2017

Epidemiologic interest in particulate matter (PM) is growing particularly because of its impact of respiratory health. It has been elucidated that PM evoked inflammatory signal in pulmonary epithelia. However, it has not been established $Ca^{2+}$ signaling mechanisms involved in acute PM-derived signaling in pulmonary fibroblasts. In the present study, we explored dust particles PM modulated intracellular $Ca^{2+}$ signaling and sought to provide a therapeutic strategy by antagonizing PM-induced intracellular $Ca^{2+}$ signaling in human lung fibroblasts MRC5 cells. We demonstrated that PM10, less than $10{\mu}m$, induced intracellular $Ca^{2+}$ signaling, which was mediated by extracellular $Ca^{2+}$. The PM10-mediated intracellular $Ca^{2+}$ signaling was attenuated by antioxidants, phospholipase blockers, polyADPR polymerase 1 inhibitor, and transient receptor potential melastatin 2 (TRPM2) inhibitors. In addition, PM-mediated increases in reactive oxygen species were attenuated by TRPM2 blockers, clotrimazole (CLZ) and N-(p-amylcinnamoyl) anthranilic acid (ACA). Our results showed that PM10 enhanced reactive oxygen species signal by measuring DCF fluorescence and the DCF signal attenuated by both TRPM2 blockers CLZ and ACA. Here, we suggest functional inhibition of TRPM2 channels as a potential therapeutic strategy for modulation of dust particle-mediated signaling and oxidative stress accompanying lung diseases.

• 동의생리병리학회지
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• 제17권3호
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• pp.791-797
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• 2003

This study investigated the effect of Yanggyuksanhwa-tang on cerebral ischemia of the rats. Considering age-related impact on cerebral ischemia, aged rats (18 months old) were used for this study. Ischemic damage was induced by the transient occlusion of bilateral common carotid arteries (BCAO) under the hypotension. Yanggyuksanhwa-tang was administered twice orally. Then changes of pyramidal neurons and heat shock protein 72 (HSP72) expressions in ischemic damaged hippocampus were of observed. The BCAO in aged rats led significant decrease of pyramidal neurons in CA1 hippocampus. While the treatment of Yanggyuksanhwa-tang significantly attenuated the reduction of pyramidal neurons in CA1 hippocampus following BCAO ischemia. The BCAO in aged rats led significant increase of HSP72 expression in CA1 and mild in CA3 hippocampus. While the treatment of Yanggyuksanhwa-tang significantly attenuated the increase of HSP72 expression in CA1 hippocampus following BCAO ischemia. The extent of HSP72 expression in CA2 and DG of hippocampus was not different between the sham operated group, the BCAO ischemia control group, and the group of Yanggyuksanhwa-tang administration after BCAO ischemia. The treatment of Yanggyuksanhwa-tang significantly attenuated the increase of normalized optical density depending on HSP72 expression in CA1 hippocampus following BCAO ischemia.

• The Korean Journal of Physiology and Pharmacology
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• 제14권1호
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• pp.45-49
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• 2010

R-type $Ca_v2.3$ high voltage-activated $Ca^{2+}$ channels in peripheral sensory neurons contribute to pain transmission. Recently we have demonstrated that, among the six $Ca_v2.3$ isoforms ($Ca_v2.3a{\sim}Ca_v2.3e$), the $Ca_v2.3e$ isoform is primarily expressed in trigeminal ganglion (TG) nociceptive neurons. In the present study, we further investigated expression patterns of $Ca_v2.3$ isoforms in the dorsal root ganglion (DRG) neurons. As in TG neurons, whole tissue RT-PCR analyses revealed the presence of two isoforms, $Ca_v2.3a$ and $Ca_v2.3e$, in DRG neurons. Single-cell RT-PCR detected the expression of $Ca_v2.3e$ mRNA in 20% (n=14/70) of DRG neurons, relative to $Ca_v2.3a$ expression in 2.8% (n=2/70) of DRG neurons. $Ca_v2.3e$ mRNA was mainly detected in small-sized neurons (n=12/14), but in only a few medium-sized neurons (n=2/14) and not in large-sized neurons, indicating the prominence of $Ca_v2.3e$ in nociceptive DRG neurons. Moreover, $Ca_v2.3e$ was preferentially expressed in tyrosine-kinase A (trkA)-positive, isolectin B4 (IB4)-negative and transient receptor potential vanilloid 1 (TRPV1)-positive neurons. These results suggest that $Ca_v2.3e$ may be the main R-type $Ca^{2+}$ channel isoform in nociceptive DRG neurons and thereby a potential target for pain treatment, not only in the trigeminal system but also in the spinal system.

• The Korean Journal of Physiology and Pharmacology
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• 제20권3호
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• pp.315-324
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• 2016

Human cardiac fibroblasts (HCFs) have various voltage-dependent $K^+$ channels (VDKCs) that can induce apoptosis. Hydrogen peroxide ($H_2O_2$) modulates VDKCs and induces oxidative stress, which is the main contributor to cardiac injury and cardiac remodeling. We investigated whether $H_2O_2$ could modulate VDKCs in HCFs and induce cell injury through this process. In whole-cell mode patch-clamp recordings, application of $H_2O_2$ stimulated $Ca^{2+}-activated$ $K^+$ ($K_{Ca}$) currents but not delayed rectifier $K^+$ or transient outward $K^+$ currents, all of which are VDKCs. $H_2O_2-stimulated$ $K_{Ca}$ currents were blocked by iberiotoxin (IbTX, a large conductance $K_{Ca}$ blocker). The $H_2O_2-stimulating$ effect on large-conductance $K_{Ca}$ ($BK_{Ca}$) currents was also blocked by KT5823 (a protein kinase G inhibitor) and 1 H-[1, 2, 4] oxadiazolo-[4, 3-a] quinoxalin-1-one (ODQ, a soluble guanylate cyclase inhibitor). In addition, 8-bromo-cyclic guanosine 3', 5'-monophosphate (8-Br-cGMP) stimulated $BK_{Ca}$ currents. In contrast, KT5720 and H-89 (protein kinase A inhibitors) did not block the $H_2O_2-stimulating$ effect on $BK_{Ca}$ currents. Using RT-PCR and western blot analysis, three subtypes of $K_{Ca}$ channels were detected in HCFs: $BK_{Ca}$ channels, small-conductance $K_{Ca}$ ($SK_{Ca}$) channels, and intermediate-conductance $K_{Ca}$ ($IK_{Ca}$) channels. In the annexin V/propidium iodide assay, apoptotic changes in HCFs increased in response to $H_2O_2$, but IbTX decreased $H_2O_2$-induced apoptosis. These data suggest that among the VDKCs of HCFs, $H_2O_2$ only enhances $BK_{Ca}$ currents through the protein kinase G pathway but not the protein kinase A pathway, and is involved in cell injury through $BK_{Ca}$ channels.

• The Korean Journal of Physiology and Pharmacology
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• 제17권3호
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• pp.223-228
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• 2013

The calcium-activated $K^+$ ($BK_{Ca}$) channel is one of the potassium-selective ion channels that are present in the nervous and vascular systems. $Ca^{2+}$ is the main regulator of $BK_{Ca}$ channel activation. The $BK_{Ca}$ channel contains two high affinity $Ca^{2+}$ binding sites, namely, regulators of $K^+$ conductance, RCK1 and the $Ca^{2+}$ bowl. Lysophosphatidic acid (LPA, 1-radyl-2-hydroxy-sn-glycero-3-phosphate) is one of the neurolipids. LPA affects diverse cellular functions on many cell types through G protein-coupled LPA receptor subtypes. The activation of LPA receptors induces transient elevation of intracellular $Ca^{2+}$ levels through diverse G proteins such as $G{\alpha}_{q/11}$, $G{\alpha}_i$, $G{\alpha}_{12/13}$, and $G{\alpha}s$ and the related signal transduction pathway. In the present study, we examined LPA effects on $BK_{Ca}$ channel activity expressed in Xenopus oocytes, which are known to endogenously express the LPA receptor. Treatment with LPA induced a large outward current in a reversible and concentration-dependent manner. However, repeated treatment with LPA induced a rapid desensitization, and the LPA receptor antagonist Ki16425 blocked LPA action. LPA-mediated $BK_{Ca}$ channel activation was also attenuated by the PLC inhibitor U-73122, $IP_3$ inhibitor 2-APB, $Ca^{2+}$ chelator BAPTA, or PKC inhibitor calphostin. In addition, mutations in RCK1 and RCK2 also attenuated LPA-mediated $BK_{Ca}$ channel activation. The present study indicates that LPA-mediated activation of the $BK_{Ca}$ channel is achieved through the PLC, $IP_3$, $Ca^{2+}$, and PKC pathway and that LPA-mediated activation of the $BK_{Ca}$ channel could be one of the biological effects of LPA in the nervous and vascular systems.

• The Korean Journal of Physiology
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• 제18권1호
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• pp.37-50
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• 1984

The effects of $Ca^{++}$ and its antagonists (verapamil and $La^{+++}$) upon the spontaneous contraction and the contracture induced by 60 mM K-Tyrode solution were studied in the isolated uterine muscle. Longitudinal muscle strips were prepared from the rat uteri at estrous stage. All experiments were performed in tris-buffered Tyrode solution which was aerated with 100% $O_2$ and kept at 35^{\circ}$. The results obtained were as follows: 1) In the uterine strips contracting spontaneously, both the amplitude of peak tension and the area of contraction curve increased dose-dependently in the range of $0.5${\sim}8$ mM $Ca^{++}$. The frequency of contraction increased as the concentration of $Ca^{++}$ increased up to 2 mM, but above this concentration the frequency decreased. In $Ca^{++}-free$ media, however, contraction did not develop. In the contracture induced by 60 mM K-Tyrode solution, the developed tension increased dose-dependently as the concentration of external $Ca^{++}$ increased to 8 mM. In the absence of external $Ca^{++}$ K-contracture appeared, but it was not sustained. 2) The spontaneous contraction of rat uterus was suppressed by verapamil in proportion to an increase of its concentration and totally abolished at the concentration of $3{\times}10^{-4}\;g/l$, but the spontaneous contraction re-appeared by addition of $Ca^{++}$. The amplitude of peak tension recovered completely but the recovery of frequency was incomplete. K-contracture decreased in a dose-dependent manner after the treatment with verapamil and totally disappeared at its concentration of $3{\times}10^{-4}\;g/l$. Even in this case contracture developed again by extra $Ca^{++}$. 3) The spontaneous contractile activity was inhibited by $La^{+++}$. At the concentration of $10^{-4}$M $La^{+++}$, fibrillation appeared. In the strip inhibited by $10^{-5}M\;La^{+++}$, contractility recovered completely by extra $Ca^{++}$ while in the $10^{-4}M\;La^{+++}$ treated preparation, the rhythmic spontaneous contraction did not develop even at the concentration of 16 mM $Ca^{++}$. After the initial transient depression of contracture tension by $10^{-3}M$ of $La^{+++}$, the strip stowed considerably large size of contracture, hardly influenced by external $Ca^{++}$ or verapamil. The results obtained in this experiment suggest that in the rat uterine muscle there would be some competitive actions between $Ca^{++}$ and its antagonists. It is speculated that $Ca^{++}$ plays an important role in the conduction of excitation, and $La^{+++}$ influences upon cellular $Ca^{++}$ mobilization and re-uptake process as well as transmembrane $Ca^{++}$ transport in a K-depolarized state.

• Applied Microscopy
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• 제19권1호
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• pp.1-18
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• 1989

허혈로 인하여 손상을 받은 심근세포의 기능을 재건하기 위하여 재관류가 반드시 이로운가하는 것에 대하여는 논란이 많다. 따라서 저자는 체중 500그람 내외의 기니피그를 실험재료로 하여 일과성허혈(10분) 및 일과성허혈후 재관류시(20분) 좌심실 심근세포의 미세구조 및 칼슘분포의 변화를 비교관찰하여 재관류가 심근세포재건에 어느정도 도움을 줄 수 있는가를 알아보고자 하였다. 대조군에서는 심근세포의 미세구조가 비교적 잘 보존되어 있었으며 심근세포막 및 사립체내에서 20nm 크기 정도의 칼슘침착을 볼 수 있었다. 이에 반하여 일과성허혈후, 대부분의 심근세포에서는 세포막손상, I 대의 확장, 사립체의 종창, 세포내 수분축적, 당원과립의 고갈, 지방소적유령(ghost)의 출현, 염색질의 응집 및 변연부로의 이동, 세포연접의 분리 등의 미세구조의 변화와 심근세포막 및 사립체내에서 칼슘침착의 현저한 감소를 볼 수 있었으나, 비가역성의 변화는 찾아 볼 수 없었다. 그러나 허혈후 재관류시 일부의 심근세포에서는 큰 변화를 보이지 않았지만, 많은 세포에서 이러한 미세구조의 변화는 보다 심해져 국소적으로 근절(sarcomere)의 과이완 및 striation pattern의 소실, 세포부종 등이 현저해졌으나, 세포막 및 사립체내에서는 대조군에서와 같이 칼슘침착이 재출현하였다. 이상의 결과로 미루어 일과성허혈후 재관류는 심근세포의 칼슘 조절기능 회복에 어느정도 도움을 줄 수 있으나 허혈성 손상을 악화시킬 가능성도 있을 것으로 생각된다.

• 동의생리병리학회지
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• 제25권2호
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• pp.300-305
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• 2011

The present study was investigated the neuroprotective effects of acupuncture at ST36 on learning and memory deficits after transient cerebral ischemia in a gerbil model. The animals were randomly divided into three groups (n=7 in each group): the sham operation group (SHAM), ischemia-induced and ST36 acupuncture group (ISC + ST36), and the ischemia-induced and Tail-acupuncture group (ISC + TAIL). For the acupuncture stimulation, stainless steel needles, 0.3 mm in diameter, were inserted bilaterally into the ST36 locus or the tail and stimulated for 1 min/day for 14 days. Using the Morris water maze test, the animals were tested on spatial learning and memory. In addition, the effects of acupuncture on memory storage and the choline acetyltransferase (ChAT) activity, in the hippocampal CA1 area, were investigated by ChAT immunohistochemistry. Transient cerebral ischemia produced impaired performance on the MWM test (DAY 5: p<0.01 and retention test: p<0.05) and severely decreased ChAT immunoreactivity in the CA1 hippocampal area compared to the SHAM group (p<0.05). However, improved learning and memory were observed (DAY 5: p<0.05 and retention test: p<0.01) as well as a significantly reduced loss of ChAT immunoactivity in the hippocampal CA1 region (p<0.001) after acupuncture stimulation at ST36 were observed. These results show that acupuncture at ST36 ameliorated the learning and memory deficits at least in part through the cholinergic system. The findings of this study provide potential data that acupuncture is useful for the treatment of some of the behavioral impairs of transient cerebral ischemia.