• The Korean Journal of Physiology and Pharmacology
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• v.4 no.6
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• pp.427-437
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• 2000

The early studies of cardiac and smooth muscle cells provided evidence for two different calcium channels, the L-type (also called high-voltage activated [HVA]) and T-type (low-voltage activated [LVA]). These calcium channels provided calcium for muscle contractions and pace-making activities. As might be expected, the number of different calcium channels increased when researchers studied neurons and the identification of the neuronal calcium channels has proven to be much more difficult than with the muscle calcium channels. There are two reasons for this difficulty; (1) a larger number of different calcium channels in neurons and (2) many of the different calcium channels have similar kinetic properties. This review uses the N-type calcium channel to illustrate the difficulties in identifying and characterizing calcium channels in neurons. It shows that the discovery of toxins that can specifically block single calcium channel types has made it possible to easily and rapidly discern the physiological roles of the different calcium channels in the neuron, Without these toxins it is unlikely that progress would have been as rapid.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.133-140
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• 2017

Conflicting evidence has been obtained regarding whether transient receptor potential cation channels (TRPC) are store-operated channels (SOCs) or receptor-operated channels (ROCs). Moreover, the Ca/Na permeability ratio differs depending on whether the current-voltage (I-V) curve has a doubly rectifying shape or inward rectifying shape. To investigate the calcium permeability of TRPC4 channels, we attached GCaMP6s to TRPC4 and simultaneously measured the current and calcium signals. A TRPC4 specific activator, (-)-englerin A, induced both current and calcium fluorescence with the similar time course. Muscarinic receptor stimulator, carbachol, also induced both current and calcium fluorescence with the similar time course. By forming heteromers with TRPC4, TRPC1 significantly reduced the inward current with outward rectifying I-V curve, which also caused the decrease of calcium fluorescence intensity. These results suggest that GCaMP6s attached to TRPC4 can detect slight calcium changes near TRPC4 channels. Consequently, TRPC4-GCaMP6s can be a useful tool for testing the calcium permeability of TRPC4 channels.

• ALGAE
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• v.36 no.4
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• pp.315-326
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• 2021

Ion channels are membrane protein complexes mediating passive ion flux across the cell membranes. Every organism has a certain set of ion channels that define its physiology. Dinoflagellates are ecologically important microorganisms characterized by effective physiological adaptability, which backs up their massive proliferations that often result in harmful blooms (red tides). In this study, we used a bioinformatics approach to identify homologs of known ion channels that belong to 36 ion channel families. We demonstrated that the versatility of the dinoflagellate physiology is underpinned by a high diversity of ion channels including homologs of animal and plant proteins, as well as channels unique to protists. The analysis of 27 transcriptomes allowed reconstructing a consensus ion channel repertoire (channelome) of dinoflagellates including the members of 31 ion channel families: inwardly-rectifying potassium channels, two-pore domain potassium channels, voltage-gated potassium channels (K_v), tandem K_v, cyclic nucleotide-binding domain-containing channels (CNBD), tandem CNBD, eukaryotic ionotropic glutamate receptors, large-conductance calcium-activated potassium channels, intermediate/small-conductance calcium-activated potassium channels, eukaryotic single-domain voltage-gated cation channels, transient receptor potential channels, two-pore domain calcium channels, four-domain voltage-gated cation channels, cation and anion Cys-loop receptors, small-conductivity mechanosensitive channels, large-conductivity mechanosensitive channels, voltage-gated proton channels, inositole-1,4,5-trisphosphate receptors, slow anion channels, aluminum-activated malate transporters and quick anion channels, mitochondrial calcium uniporters, voltage-dependent anion channels, vesicular chloride channels, ionotropic purinergic receptors, animal volage-insensitive cation channels, channelrhodopsins, bestrophins, voltage-gated chloride channels H⁺/Cl^- exchangers, plant calcium-permeable mechanosensitive channels, and trimeric intracellular cation channels. Overall, dinoflagellates represent cells able to respond to physical and chemical stimuli utilizing a wide range of G-protein coupled receptors- and Ca²⁺-dependent signaling pathways. The applied approach not only shed light on the ion channel set in dinoflagellates, but also provided the information on possible molecular mechanisms underlying vital cellular processes dependent on the ion transport.

• Biomolecules & Therapeutics
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• v.26 no.5
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• pp.439-445
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• 2018

T-type calcium channels are low voltage-activated calcium channels that evoke small and transient calcium currents. Recently, T-type calcium channels have been implicated in neurodevelopmental disorders such as autism spectrum disorder and neural tube defects. However, their function during embryonic development is largely unknown. Here, we investigated the function and expression of T-type calcium channels in embryonic neural progenitor cells (NPCs). First, we compared the expression of T-type calcium channel subtypes (CaV3.1, 3.2, and 3.3) in NPCs and differentiated neural cells (neurons and astrocytes). We detected all subtypes in neurons but not in astrocytes. In NPCs, CaV3.1 was the dominant subtype, whereas CaV3.2 was weakly expressed, and CaV3.3 was not detected. Next, we determined CaV3.1 expression levels in the cortex during early brain development. Expression levels of CaV3.1 in the embryonic period were transiently decreased during the perinatal period and increased at postnatal day 11. We then pharmacologically blocked T-type calcium channels to determine the effects in neuronal cells. The blockade of T-type calcium channels reduced cell viability, and induced apoptotic cell death in NPCs but not in differentiated astrocytes. Furthermore, blocking T-type calcium channels rapidly reduced AKT-phosphorylation (Ser473) and $GSK3{\beta}$-phosphorylation (Ser9). Our results suggest that T-type calcium channels play essential roles in maintaining NPC viability, and T-type calcium channel blockers are toxic to embryonic neural cells, and may potentially be responsible for neurodevelopmental disorders.

• BMB Reports
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• v.53 no.3
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• pp.125-132
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• 2020

Transient receptor potential (TRP) channels comprise a diverse family of ion channels, the majority of which are calcium permeable and show sophisticated regulatory patterns in response to various environmental cues. Early studies led to the recognition of TRP channels as environmental and chemical sensors. Later studies revealed that TRP channels mediated the regulation of intracellular calcium. Mutations in TRP channel genes result in abnormal regulation of TRP channel function or expression, and interfere with normal spatial and temporal patterns of intracellular local Ca²⁺ distribution. The resulting dysregulation of multiple downstream effectors, depending on Ca²⁺ homeostasis, is associated with hallmarks of cancer pathophysiology, including enhanced proliferation, survival and invasion of cancer cells. These findings indicate that TRP channels affect multiple events that control cellular fate and play a key role in cancer progression. This review discusses the accumulating evidence supporting the role of TRP channels in tumorigenesis, with emphasis on prostate cancer.

• Proceedings of the Korean Biophysical Society Conference
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• 2002.06b
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• pp.38-38
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• 2002

Whole-cell recordings from adult rat sympathetic neurons demonstrate that calcium current is comprised of at least three types, N, L '||'&'||' R. We are using cell-attached patch recording to identify the single calcium channels that underlie these macroscopic currents. Single channels were resolved the presence of 100 mM Ba$\^$2＋/ and l${\mu}$M BayK 8644 over the voltage range -40 to $\^$＋/50 mV.(omitted)

• BMB Reports
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• v.56 no.3
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• pp.172-177
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• 2023

BEST family is a class of Ca²⁺-activated Cl- channels evolutionary well conserved from bacteria to human. The human BEST paralogs (BEST1-BEST4) share significant amino acid sequence homology in the N-terminal region, which forms the transmembrane helicases and contains the direct calcium-binding site, Ca²⁺-clasp. But the cytosolic C-terminal region is less conserved in the paralogs. Interestingly, this domain-specific sequence conservation is also found in the BEST1 orthologs. However, the functional role of the C-terminal region in the BEST channels is still poorly understood. Thus, we aimed to understand the functional role of the C-terminal region in the human and mouse BEST1 channels by using electrophysiological recordings. We found that the calcium-dependent activation of BEST1 channels can be modulated by the C-terminal region. The C-terminal deletion hBEST1 reduced the Ca²⁺-dependent current activation and the hBEST1-mBEST1 chimera showed a significantly reduced calcium sensitivity to hBEST1 in the HEK293 cells. And the C-terminal domain could regulate cellular expression and plasma membrane targeting of BEST1 channels. Our results can provide a basis for understanding the C-terminal roles in the structure-function of BEST family proteins.

• Clinical and Experimental Pediatrics
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• v.57 no.10
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• pp.445-450
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• 2014

Purpose: Familial hypokalemic periodic paralysis (HOKPP) is an autosomal dominant channelopathy characterized by episodic attacks of muscle weakness and hypokalemia. Mutations in the calcium channel gene, CACNA1S, or the sodium channel gene, SCN4A, have been found to be responsible for HOKPP; however, the mechanism that causes hypokalemia remains to be determined. The aim of this study was to improve the understanding of this mechanism by investigating the expression of calcium-activated potassium ($K_{Ca}$) channel genes in HOKPP patients. Methods: We measured the intracellular calcium concentration with fura-2-acetoxymethyl ester in skeletal muscle cells of HOKPP patients and healthy individuals. We examined the mRNA and protein expression of KCa channel genes (KCNMA1, KCNN1, KCNN2, KCNN3, and KCNN4) in both cell types. Results: Patient cells exhibited higher cytosolic calcium levels than normal cells. Quantitative reverse transcription polymerase chain reaction analysis showed that the mRNA levels of the $K_{Ca}$ channel genes did not significantly differ between patient and normal cells. However, western blot analysis showed that protein levels of the KCNMA1 gene, which encodes $K_{Ca}$1.1 channels (also called big potassium channels), were significantly lower in the membrane fraction and higher in the cytosolic fraction of patient cells than normal cells. When patient cells were exposed to 50 mM potassium buffer, which was used to induce depolarization, the altered subcellular distribution of BK channels remained unchanged. Conclusion: These findings suggest a novel mechanism for the development of hypokalemia and paralysis in HOKPP and demonstrate a connection between disease-associated mutations in calcium/sodium channels and pathogenic changes in nonmutant potassium channels.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.3
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• pp.277-289
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• 2018

The exponential increase in the use of mobile communication has triggered public concerns about the potential adverse effects of radiofrequency electromagnetic fields (RF-EMF) emitted by mobile phones on the central nervous system (CNS). In this study, we explored the relationship between calcium channels and apoptosis or autophagy in the hippocampus of C57BL/6 mice after RF-EMF exposure with a specific absorption rate (SAR) of 4.0 W/kg for 4 weeks. Firstly, the expression level of voltage-gated calcium channels (VGCCs), a key regulator of the entry of calcium ions into the cell, was confirmed by immunoblots. We investigated and confirmed that pan-calcium channel expression in hippocampal neurons were significantly decreased after exposure to RF-EMF. With the observed accumulation of autolysosomes in hippocampal neurons via TEM, the expressions of autophagy-related genes and proteins (e.g., LC3B-II) had significantly increased. However, down-regulation of the apoptotic pathway may contribute to the decrease in calcium channel expression, and thus lower levels of calcium in hippocampal neurons. These results suggested that exposure of RF-EMF could alter intracellular calcium homeostasis by decreasing calcium channel expression in the hippocampus; presumably by activating the autophagy pathway, while inhibiting apoptotic regulation as an adaptation process for 835 MHz RF-EMF exposure.

• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.389-396
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• 2020

Valproic acid is a clinically used mood stabilizer and antiepileptic drug. Valproic acid has been suggested as a teratogen associated with the manifestation of neurodevelopmental disorders, such as fetal valproate syndrome and autism spectrum disorders, when taken during specific time window of pregnancy. Previous studies proposed that prenatal exposure to valproic acid induces abnormal proliferation and differentiation of neural progenitor cells, presumably by inhibiting histone deacetylase and releasing the condensed chromatin structure. Here, we found valproic acid up-regulates the transcription of T-type calcium channels by inhibiting histone deacetylase in neural progenitor cells. The pharmacological blockade of T-type calcium channels prevented the increased proliferation of neural progenitor cells induced by valproic acid. Differentiated neural cells from neural progenitor cells treated with valproic acid displayed increased levels of calcium influx in response to potassium chloride-induced depolarization. These results suggest that prenatal exposure to valproic acid up-regulates T-type calcium channels, which may contribute to increased proliferation of neural progenitor cells by inducing an abnormal calcium response and underlie the pathogenesis of neurodevelopmental disorders.