• Journal of Life Science
• /
• v.14 no.5
• /
• pp.882-890
• /
• 2004

Gap junction is a membrane structure facilitating the direct transmission of several ions and small molecules between two cells. It is also called an 'intercellular channel' to distinguish it from other well-known cellular channels (e.g. sodium and potassium channels). Gap junction channels are not passive conduits, rather the ion channels modulated by several stimuli including pH, calcium ion, voltage, and a chemical modification (mainly known as phosphorylation). Among them, the effects of voltage on the gating of gap junction channels have been well studied. Gap junction channels are more sensitive to the transjunctional potential ($V_j$) between two cells rather than the membrane potential($V_m$) between inside and outside the cell. In this review, I will summarize the general properties of gap junction channel and discuss the gating mechanism for the gap channels.

• Progress in Medical Physics
• /
• v.12 no.1
• /
• pp.59-70
• /
• 2001

Adrenal chromaffin cells secrete catecholamine in response to acetylcholine. The secretory response has absolute requirement for extracellular calcium, indicating that $Ca^{2+}$ influx through voltage operated $Ca^{2+}$ channels is the primary trigger of the secretion cascade. Although the existence of various types of $Ca^{2+}$ channels has been explored using patch clamp technique in adrenal chromaffin cells, there is still disagreement with the types of $Ca^{2+}$ channels existed in different species. Therefore, we have tried to identify several distinct types of $Ca^{2+}$ channels in rat chromaffin cells. By using nicardipine(L type channel blocker), $\omega$-CgTx GVIA(N type channel blocker), and $\omega$-AgaTx VIA(P type channel blocker), it was identified that L, N, and P type $Ca^{2+}$ channel exist in rat adrenal chromaffin cells and the order of contribution of each channel type to whole cell $Ca^{2+}$ current was L type> N type> P type. type> P type.

• The Korean Journal of Physiology and Pharmacology
• /
• v.18 no.5
• /
• pp.377-381
• /
• 2014

Propofol is a widely used anesthetic. Many studies have shown that propofol has direct effects on blood vessels, but the precise mechanism is not fully understood. Secondary intrapulmonary artery rings from male rats were prepared and mounted in a Multi Myograph System. The following constrictors were used to induce contractions in isolated artery rings: high $K^+$ solution (60 mmol/L); U46619 solution (100 nmol/L); 5-hydroxytryptamine (5-HT; $3{\mu}mol/L$); or phenylephrine (Phe; $1{\mu}mol/L$). The relaxation effects of propofol were tested on high $K^+$ or U46619 precontracted rings. Propofol also was added to induce relaxation of rings preconstricted by U46619 after pretreatment with the nitric oxide synthase inhibitor $N^G$-nitro-L-arginine methyl ester (L-NAME). The effects of propofol on $Ca^{2+}$ influx via the L-type $Ca^{2+}$ channels were evaluated by examining contraction-dependent responses to $CaCl_2$ in the absence or presence of propofol (10 to $300{\mu}mol/L$). High $K^+$ solution and U46619 induced remarkable contractions of the rings, whereas contractions induced by 5-HT and Phe were weak. Propofol induced dose-dependent relaxation of artery rings precontracted by the high $K^+$ solution. Propofol also induced relaxation of rings precontracted by U46619 in an endothelium-independent way. Propofol at different concentrations significantly inhibited the $Ca^{2+}$-induced contractions of pulmonary rings exposed to high $K^+$-containing and $Ca^{2+}$-free solution in a dose-dependent manner. Propofol relaxed vessels precontracted by the high $K^+$ solution and U46619 in an endothelium-independent way. The mechanism for this effect may involve inhibition of calcium influx through voltage-operated calcium channels (VOCCs) and receptor-operated calcium channels (ROCCs).

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.29 no.4
• /
• pp.305-312
• /
• 2015

Paeonol is a major component found in the Paeoniaceae family such as Paeonia suffruticosa Andrews. Paeonia suffruticosa Andrews has traditionally been used to enhance blood flow and relieve joint pain in east Asian countries including China, Korea and Japan. Current research has shown that paeonol blocked the voltage-gated sodium channel and L-type calcium channel. However, there is a lack of research to reveal the relation between cardiac function and blockade of ion channels by paeonol. Therefore, the aim of this study is to investigate whether paeonol has anti-arrhythmic effects via modulating cardiac ion channels. It is collected that the effects of paeonol on multiple ion channels such as the fast sodium channel and L-type calcium channel from published papers. To incorporate the information on multi-channel block, we computed the effects using the mathematical cardiac model of the guinea-pig and rat ventricular cells (Noble 1998 and 1991 model) and induced early after-depolarizations (EADs) to generate an arrhythmia in the whole heart. Paeonol slightly shortened the action potential duration in the normal cardiac ventricular action potential by the inhibition of sodium channel and L-type calcium channel. Paeonol presented the protective effect from EADs by the inactivation of sodium channel but not L-type calcium channel. Paeonol did not show any changes when it treated on normal ventricular cells through the inhibition of sodium channel, but the protective effect of paeonol through sodium channel on EADs was dose-dependent. These findings suggest that paeonol and its original plant may possess anti-arrhythmic activity, which implies their cardioprotective effects.

• Development and Reproduction
• /
• v.24 no.4
• /
• pp.297-306
• /
• 2020

Repetitive changes in the intracellular calcium concentration ([Ca²⁺]i) triggers egg activation, including cortical granule exocytosis, resumption of second meiosis, block to polyspermy, and initiating embryonic development. [Ca²⁺]i oscillations that continue for several hours, are required for the early events of egg activation and possibly connected to further development to the blastocyst stage. The sources of Ca²⁺ ion elevation during [Ca²⁺]i oscillations are Ca²⁺ release from endoplasmic reticulum through inositol 1,4,5 tri-phosphate receptor and Ca²⁺ ion influx through Ca²⁺ channel on the plasma membrane. Ca²⁺ channels have been characterized into voltage-dependent Ca²⁺ channels (VDCCs), ligand-gated Ca²⁺ channel, and leak-channel. VDCCs expressed on muscle cell or neuron is specified into L, T, N, P, Q, and R type VDCs by their activation threshold or their sensitivity to peptide toxins isolated from cone snails and spiders. The present study was aimed to investigate the localization pattern of N and P/Q type voltage-dependent calcium channels in mouse eggs and the role in fertilization. [Ca²⁺]i oscillation was observed in a Ca²⁺ contained medium with sperm factor or adenophostin A injection but disappeared in Ca²⁺ free medium. Ca²⁺ influx was decreased by Lat A. N-VDCC specific inhibitor, ω-Conotoxin CVIIA induced abnormal [Ca²⁺]i oscillation profiles in SrCl₂ treatment. N or P/Q type VDC were distributed on the plasma membrane in cortical cluster form, not in the cytoplasm. Ca²⁺ influx is essential for [Ca²⁺]i oscillation during mammalian fertilization. This Ca²⁺ influx might be controlled through the N or P/Q type VDCCs. Abnormal VDCCs expression of eggs could be tested in fertilization failure or low fertilization eggs in subfertility women.

• BMB Reports
• /
• v.33 no.3
• /
• pp.202-207
• /
• 2000

The depletion of intracellular calcium stores by thapsigargin treatment evoked extracellular calcium-dependent membrane currents in Xenopus laevis oocytes. These currents have been compared to those evoked by microinjection of a calcium influx factor (CIF) purified from Jurkat T lymphocytes. The membrane currents elicited by thapsigargin treatment (peak current, $163{\pm}60$ nA) or CIF injection (peak current, $897{\pm}188$ nA) were both dependent on calcium entry, based on their eradication by the removal of extracellular calcium. The currents were, in both cases, attributed primarily to well-characterized $Ca^{2+}-dependent$ $Cl^-$ currents, based on their similar reversal potentials (-24 mV vs. -28 mV) and their inhibition by niflumic acid (a $Cl^-$ channel blocker). Currents induced by either thapsigargin treatment or CIF injection exhibited an identical pattern of inhibitory sensitivity to a panel of lanthanides, suggesting that thapsigargin treatment or CIF injection evoked $Cl^-$ currents by stimulating calcium influx through pharmacologically identical calcium channels. These results indicate that CIF acts on the same calcium entry pathway activated by the depletion of calcium stores and most lanthanides are novel pharmacological tools for the study of calcium entry in Xenopus oocytes.

• The Korean Journal of Physiology and Pharmacology
• /
• v.23 no.5
• /
• pp.357-366
• /
• 2019

$G{\alpha}_q$-coupled receptor stimulation was implied in the activation process of transient receptor potential canonical (TRPC)1/4 and TRPC1/5 heterotetrameric channels. The inactivation occurs due to phosphatidylinositol 4,5-biphosphate ($PI(4,5)P_2$) depletion. When $PI(4,5)P_2$ depletion was induced by muscarinic stimulation or inositol polyphosphate 5-phosphatase (Inp54p), however, the inactivation by muscarinic stimulation was greater compared to that by Inp54p. The aim of this study was to investigate the complete inactivation mechanism of the heteromeric channels upon $G{\alpha}_q$-phospholipase $C{\beta}$ ($G{\alpha}_q-PLC{\beta}$) activation. We evaluated the activity of heteromeric channels with electrophysiological recording in HEK293 cells expressing TRPC channels. TRPC1/4 and TRPC1/5 heteromers undergo further inhibition in $PLC{\beta}$ activation and calcium/protein kinase C (PKC) signaling. Nevertheless, the key factors differ. For TRPC1/4, the inactivation process was facilitated by $Ca^{2+}$ release from the endoplasmic reticulum, and for TRPC1/5, activation of PKC was concerned mostly. We conclude that the subsequent increase in cytoplasmic $Ca^{2+}$ due to $Ca^{2+}$ release from the endoplasmic reticulum and activation of PKC resulted in a second phase of channel inhibition following $PI(4,5)P_2$ depletion.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1994.04a
• /
• pp.217-217
• /
• 1994

Calcium entry blockers, capable of inhibiting transmembrane influx of extracellular calcium through specific calcium channels, are useful drugs in the treatment of angina pectoris, hypertension, cardiac arrythmia, and various cardiovascular disorders. Compounds having isoquinoline structures have recently been reported to possess calcium antagonistic action. Therefore, in the present study, we have attempted to synthesize some isoquinoline and related compound.; in order to search for potentially effective chemicals acting on cardiovascular system, and evaluated their pharmacological properties focusing on calcium antagonistic actions. Almost all of the compounds so far synthesized, had inhibitory action against phenylephrine or high potassium-induced contraction in vascular smooth muscle with different degrees of potencies depending on their structures, However, some of tetrahydroisoquinoline analogs showed directly inhibit calcium current in isolated rabbit cardiac myocytes examined by patch clamp techniques. The pharmacological properties of these compounds need more intensive investigation as to whether these chemicals may have developed as a new cardiovascular active drugs. Therefore, we are now under investigation of the mechanism of action of these compounds.

• The Korean Journal of Physiology and Pharmacology
• /
• v.24 no.3
• /
• pp.277-286
• /
• 2020

Polycystic kidney disease 2-like-1 (PKD2L1), also known as polycystin-L or TRPP3, is a non-selective cation channel that regulates intracellular calcium concentration. Calmodulin (CaM) is a calcium binding protein, consisting of N-lobe and C-lobe with two calcium binding EF-hands in each lobe. In previous study, we confirmed that CaM is associated with desensitization of PKD2L1 and that CaM N-lobe and PKD2L1 EF-hand specifically are involved. However, the CaM-binding domain (CaMBD) and its inhibitory mechanism of PKD2L1 have not been identified. In order to identify CaM-binding anchor residue of PKD2L1, single mutants of putative CaMBD and EF-hand deletion mutants were generated. The current changes of the mutants were recorded with whole-cell patch clamp. The calmidazolium (CMZ), a calmodulin inhibitor, was used under different concentrations of intracellular. Among the mutants that showed similar or higher basal currents with that of the PKD2L1 wild type, L593A showed little change in current induced by CMZ. Co-expression of L593A with CaM attenuated the inhibitory effect of PKD2L1 by CaM. In the previous study it was inferred that CaM C-lobe inhibits channels by binding to PKD2L1 at 16 nM calcium concentration and CaM N-lobe at 100 nM. Based on the results at 16 nM calcium concentration condition, this study suggests that CaM C-lobe binds to Leu-593, which can be a CaM C-lobe anchor residue, to regulate channel activity. Taken together, our results provide a model for the regulation of PKD2L1 channel activity by CaM.

• Journal of Korean Dental Science
• /
• v.10 no.2
• /
• pp.45-52
• /
• 2017

Calcium has versatile roles in diverse physiological functions. Among these functions, intracellular $Ca^{2+}$ plays a key role during the secretion of salivary glands. In this review, we introduce the diverse cellular components involved in the saliva secretion and related dynamic intracellular $Ca^{2+}$ signals. Calcium acts as a critical second messenger for channel activation, protein translocation, and volume regulation, which are essential events for achieving the salivary secretion. In the secretory process, $Ca^{2+}$ activates $K^+$ and $Cl^-$ channels to transport water and electrolyte constituting whole saliva. We also focus on the $Ca^{2+}$ signals from intracellular stores with discussion about detailed molecular mechanism underlying the generation of characteristic $Ca^{2+}$ patterns. In particular, inositol triphosphate signal is a main trigger for inducing $Ca^{2+}$ signals required for the salivary gland functions. The biphasic response of inositol triphosphate receptor and $Ca^{2+}$ pumps generate a self-limiting pattern of $Ca^{2+}$ efflux, resulting in $Ca^{2+}$ oscillations. The regenerative $Ca^{2+}$ oscillations have been detected in salivary gland cells, but the exact mechanism and function of the signals need to be elucidated. In future, we expect that further investigations will be performed toward better understanding of the spatiotemporal role of $Ca^{2+}$ signals in regulating salivary secretion.