• Title/Summary/Keyword: activated calcium

Search Result 361, Processing Time 0.026 seconds

Carbon monoxide activates large-conductance calcium-activated potassium channels of human cardiac fibroblasts through various mechanisms

  • Bae, Hyemi;Kim, Taeho;Lim, Inja
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.25 no.3
    • /
    • pp.227-237
    • /
    • 2021
  • Carbon monoxide (CO) is a cardioprotectant and potential cardiovascular therapeutic agent. Human cardiac fibroblasts (HCFs) are important determinants of myocardial structure and function. Large-conductance Ca2+-activated K+ (BK) channel is a potential therapeutic target for cardiovascular disease. We investigated whether CO modulates BK channels and the signaling pathways in HCFs using whole-cell mode patch-clamp recordings. CO-releasing molecules (CORMs; CORM-2 and CORM-3) significantly increased the amplitudes of BK currents (IBK). The CO-induced stimulating effects on IBK were blocked by pre-treatment with specific nitric oxide synthase (NOS) blockers (L-NG-monomethyl arginine citrate and L-NG-nitroarginine methyl ester). 8-bromo-cyclic GMP increased IBK. KT5823 (inhibits PKG) or ODQ (inhibits soluble guanylate cyclase) blocked the CO-stimulating effect on IBK. Moreover, 8-bromo-cyclic AMP also increased IBK, and pre-treatment with KT5720 (inhibits PKA) or SQ22536 (inhibits adenylate cyclase) blocked the CO effect. Pre-treatment with N-ethylmaleimide (a thiol-alkylating reagent) also blocked the CO effect on IBK, and DL-dithiothreitol (a reducing agent) reversed the CO effect. These data suggest that CO activates IBK through NO via the NOS and through the PKG, PKA, and S-nitrosylation pathways.

Antihyperalgesic Effects of Ethosuximide and Mibefradil, T-type Voltage Activated Calcium Channel Blockers, in a Rat Model of Postoperative Pain (흰쥐의 술 후 통증 모델에서 T형 칼슘 통로 차단제인 Ethosuximide와 Mibefradil의 항통각과민 효과)

  • Shinn, Helen Ki;Cha, Young Deog;Han, Jeong Uk;Yoon, Jeong Won;Kim, Boo Seong;Song, Jang Ho
    • The Korean Journal of Pain
    • /
    • v.20 no.2
    • /
    • pp.92-99
    • /
    • 2007
  • Background: A correlation between a T-type voltage activated calcium channel (VACC) and pain mechanism has not yet been established. The purpose of this study is to find out the effect of ethosuximide and mibefradil, representative selective T-type VACC blockers on postoperative pain using an incisional pain model of rats. Methods: After performing a plantar incision, rats were stabilized on plastic mesh for 2 hours. Then, the rats were injected with ethosuximide or mibefradil, intraperitoneally and intrathecally. The level of withdrawal threshold to the von Frey filament near the incision site was determined and the dose response curves were obtained. Results: After an intraperitoneal ethosuximide or mibefradil injection, the dose-response curve showed a dose-dependent increase of the threshold in a withdrawal reaction. After an intrathecal injection of ethosuximide, the threshold of a withdrawal reaction to mechanical stimulation increased and the increase was dose-dependent. After an intrathecal injection of mibefradil, no change occurred in either the threshold of a withdrawal reaction to mechanical stimulation or a dose-response curve. Conclusions: The T-type VACC blockers in a rat model of postoperative pain showed the antihyperalgesic effect. This effect might be due to blockade of T-type VACC, which was distributed in the peripheral nociceptors or at the supraspinal level. Further studies of the effect of T-type VACC on a pain transmission mechanism at the spinal cord level would be needed.

Hardening Properties of Activated Calcium Dialuminate Clinker with Phosphoric Acid Solution

  • Song, Tae-Woong;Kim, Sei-Gi
    • The Korean Journal of Ceramics
    • /
    • v.3 no.4
    • /
    • pp.235-238
    • /
    • 1997
  • Basic properties of new cement pastes based on the system $CaO-Al_2O_3-P_O_5-H_2O$were studied Phosphoric acid solutions and calcium dialuminate clinkers synthesized by the hydration-burning method were used for liquid and powder components of the paste, respectively Variation in the compositions of the paste was achieved by changing the liquid/powder ratio and the concentration of phosphoric acid solution. The hardening rate of the paste was so largely affected by the amount of phosphoric acid that hardening was inhibited with the low-concentrated solution but was explosively accelerated with the high-concentrated solution. The phosphoric acid solutions of concentration of 45~50% and the liquid/powder ratio of 0.5~1.5 were favoured for the high early-strength cement paste with the reasonable hardening rate and high strength. The binding phase of hardened paste was the dense amorphous gel of the system $CaO-Al_2O_3-P_O_5-H_2O$. in which the unreacted calcium dialuminate grains were embeded.

  • PDF

Modulation of Cloned T-type Calcium Channels

  • Jeong, Seong-Woo
    • Proceedings of the Korean Biophysical Society Conference
    • /
    • 2002.06b
    • /
    • pp.20-21
    • /
    • 2002
  • The inflow of Ca$\^$2+/ through voltage-activated T-type calcium channels (T-channels) regulates a variety of cellular functions including neuronal excitability, cardiac pacemaker activity, hormone secretion, smooth muscle contraction, and fertilization. Not only are T-channels enormously important for the normal operation of cells, they also playa critical role in pathophysiological conditions such as cardiac hypertrophy and absence epilepsy.(omitted)

  • PDF

Effects of GS-386 on the calcium current in rabbit atrial myocytes (GS-386이 단일 심근 세포의 Ca2+ 전류에 미치는 효과)

  • Park, Choon-ok;Chang, Kyeong-jae;Kim, Yang-mi;Haan, Jae-hee;Hong, Seong-geun
    • Korean Journal of Veterinary Research
    • /
    • v.34 no.1
    • /
    • pp.37-47
    • /
    • 1994
  • The effects of the novel compound GS-386 on the calcium current were investigated in rabbit atrial myocytes. The calcium current was recorded during various depolarizations of 200 ms duration from a holding potential of -40 mV using the whole cell patch clamp technique. The calcium current was activated from -30 mV, reached maximum amplitude at +10 mV and almost disappeared at +50 mV. Superfusion of GS-386 led to a reduction of the calcium current amplitude dose-dependently and $ED_{50}$ was $2.5{\times}10^{-7}M$. But the dependence of the calcium current on the membrane potential was not altered by GS-386. The inactivation of the calcium currents showed single exponential curves in both before and after application of GS-386. The inactivation time constants before and after application of GS-386 were almost the same(35 ms and 32.5 ms). The steady-state inactivation curve of the calcium current was not shifted by GS-386. The calcium currents both before and after application of GS-386 recovered completely in 1 sec and the recovery time constants were about 200 ms in both cases. From the above results it is concluded that the novel compound GS-386 has calcium antagonistic property decreasing the calcium current.

  • PDF

NITRIC OXIDE (NO) DIRECTLY ACTIVATES CALCIUM-ACTIVATED POTASSIUM CHANNELS FROM RAT BRAIN RECONSTITUTED INTO PLANAR LIPID BILAYER

  • Shin, Jung-Hoon;Suh, Chang-Kook;Sungkwon Chung;Uhm, Dae-Yong
    • Proceedings of the Korean Biophysical Society Conference
    • /
    • 1996.07a
    • /
    • pp.35-35
    • /
    • 1996
  • Nitric oxide (NO) has been reported to have many roles in vivo ranging from the neurotransmitter in brain to the relaxant in smooth muscles. Recently, using inside-out patches, Bolotina et al. (1) showed that relaxing effect of NO is aortic smooth muscle is through direct activation of Ca2+-activated K+ channels (maxi-K), resulting in hyperpolarization. (omitted)

  • PDF

Docosahexaenoic acid reduces adenosine triphosphate-induced calcium influx via inhibition of store-operated calcium channels and enhances baseline endothelial nitric oxide synthase phosphorylation in human endothelial cells

  • Vu, Thom Thi;Dieterich, Peter;Vu, Thu Thi;Deussen, Andreas
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.23 no.5
    • /
    • pp.345-356
    • /
    • 2019
  • Docosahexaenoic acid (DHA), an omega-3-fatty acid, modulates multiple cellular functions. In this study, we addressed the effects of DHA on human umbilical vein endothelial cell calcium transient and endothelial nitric oxide synthase (eNOS) phosphorylation under control and adenosine triphosphate (ATP, $100{\mu}M$) stimulated conditions. Cells were treated for 48 h with DHA concentrations from 3 to $50{\mu}M$. Calcium transient was measured using the fluorescent dye Fura-2-AM and eNOS phosphorylation was addressed by western blot. DHA dose-dependently reduced the ATP stimulated $Ca^{2+}$-transient. This effect was preserved in the presence of BAPTA (10 and $20{\mu}M$) which chelated the intracellular calcium, but eliminated after withdrawal of extracellular calcium, application of 2-aminoethoxy-diphenylborane ($75{\mu}M$) to inhibit store-operated calcium channel or thapsigargin ($2{\mu}M$) to delete calcium store. In addition, DHA ($12{\mu}M$) increased ser1177/thr495 phosphorylation of eNOS under baseline conditions but had no significant effect on this ratio under conditions of ATP stimulation. In conclusion, DHA dose-dependently inhibited the ATP-induced calcium transient, probably via store-operated calcium channels. Furthermore, DHA changed eNOS phosphorylation suggesting activation of the enzyme. Hence, DHA may shift the regulation of eNOS away from a $Ca^{2+}$ activated mode to a preferentially controlled phosphorylation mode.

Calcium-activated Ionic Currents in Smooth Muscle Cells from Rabbit Superior Mesenteric Artery

  • Lee, Moo-Yeol;Bang, Hyo-Weon;Uhm, Dae-Yong;Rhee, Sang-Don
    • The Korean Journal of Physiology
    • /
    • v.28 no.2
    • /
    • pp.151-157
    • /
    • 1994
  • Intracellular free $Ca^{2+}$ contributes to regulation of various events occurring in vascular smooth muscle cells. One of these events is modulating the membrane iou currents. Single smooth muscle cells were isolated from rabbit mesenteric artery. Three kinds of $Ca^{2+}-activated\;current$ were studied with the patch clamp method. $Ca^{2+}-activated\;K^+\;current$ with a large oscillation was recorded in the depolarized potential range. The single channel conductance of this current was about 250 pS. It was abolished by replacing intracellular $K^+\;with\;Cs^+$. A $Ca^{2+}-activated$ nonselective cation current was observed in both the depolarized and hyperpolarized potential ranges. And it was blocked by replacement of extracellular $Na^+$ with N-methylglucamine (NMG) or extracellular application of $Cd^{2+}$. $Ca^{2+}-activated\;Cl^-\;current$ was revealed in the whole voltage range and was blocked by niflumic acid. These results indicate that at least three kinds of $Ca^{2+}-activated$ ionic currents exist in smooth muscle cells from rabbit superior mesenteric artery.

  • PDF