• The Korean Journal of Physiology and Pharmacology
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• v.4 no.4
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• pp.271-274
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• 2000

• Journal of Yeungnam Medical Science
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• v.11 no.2
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• pp.363-374
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• 1994

The purpose of this study was to investigate the characteristics or the potassium channels existing in the rat urinary bladders. Smooth muscle strips of rat detrusor urinae were examined by isometric myography. Relaxation responses of detrusor muscle strips to the three potassium channel openers pinacidil, a cyanoguanidine derivative, BRL 38227, a benzopyran derivative and RP 52891, a tertrahydrothiopyran derivative were examined. The potassium channel openers reduced the basal tone, and the rank order of potency was RP 52891>pincidil>BRL 38227. Procaine, an inhibitor of the voltage-sensitive potassium channel tended to increase the basal tone, but it did not affect the relaxant effects of the calcium-activated potassium channel opener did not antagonize the relaxant effects, but it reduced the Emax of RP 52891 and BRL 38227. Glibenclamide, an inhibitor of the ATP-sensitive potassium channel, antagonized the relaxant effects of pinacidil, RP 52891 and BRL 38227 reducing the Emax of RP 52891 and BRl 38227. Galanin which inhibits secretion of insulin through opening the ATP-sensitive potassium channels in pancreatic ${\beta}$-cells rather increased the basal tone of the isolated detrusor strips. These results suggest that the urinary bladder of the rat has mainly the ATP-sensitive, glibenclamide sensitive potassium channel, which is a different type from that in the pancreatic ${\beta}$-islet cells..

• Molecules and Cells
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• v.20 no.2
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• pp.235-240
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• 2005

Extracts of pine needles (Pinus densiflora Sieb. et Zucc.) have diverse physiological and pharmacological actions. In this study we show that pine needle extract alters pacemaker currents in interstitial cells of Cajal (ICC) by modulating ATP-sensitive $K^+$ channels and that this effect is mediated by prostaglandins. In whole cell patches at $30^{\circ}C$, ICC generated spontaneous pacemaker potentials in the current clamp mode (I = 0), and inward currents (pacemaker currents) in the voltage clamp mode at a holding potential of -70 mV. Pine needle extract hyperpolarized the membrane potential, and in voltage clamp mode decreased both the frequency and amplitude of the pacemaker currents, and increased the resting currents in the outward direction. It also inhibited the pacemaker currents in a dose-dependent manner. Because the effects of pine needle extract on pacemaker currents were the same as those of pinacidil (an ATP-sensitive $K^+$ channel opener) we tested the effect of glibenclamide (an ATP-sensitive $K^+$ channels blocker) on ICC exposed to pine needle extract. The effects of pine needle extract on pacemaker currents were blocked by glibenclamide. To see whether production of prostaglandins (PGs) is involved in the inhibitory effect of pine needle extract on pacemaker currents, we tested the effects of naproxen, a non-selective cyclooxygenase (COX-1 and COX-2) inhibitor, and AH6809, a prostaglandin EP1 and EP2 receptor antagonist. Naproxen and AH6809 blocked the inhibitory effects of pine needle extract on ICC. These results indicate that pine needle extract inhibits the pacemaker currents of ICC by activating ATP-sensitive $K^+$ channels via the production of PGs.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.1
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• pp.15-23
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• 2003

Cellular redox state is known to be perturbed during ischemia and that $Ca^{2+}$ and $K^2$ channels have been shown to have functional thiol groups. In this study, the properties of thiol redox modulation of the ATP-sensitive $K^2$ ($K_{ATP}$) channel were examined in rabbit ventricular myocytes. Rabbit ventricular myocytes were isolated using a Langendorff column for coronary perfusion and collagenase. Single-channel currents were measured in excised membrane patch configuration of patch-clamp technique. The thiol oxidizing agent 5,5'-dithio-bis-(2-nitro-benzoic acid) (DTNB) inhibited the channel activity, and the inhibitory effect of DTNB was reversed by dithiothreitol (disulfide reducing agent; DTT). DTT itself did not have any effect on the channel activity. However, in the patches excised from the metabolically compromised cells, DTT increased the channel activity. DTT had no effect on the inhibitory action by ATP, showing that thiol oxidation was not involved in the blocking mechanism of ATP. There were no statistical difference in the single channel conductance for the oxidized and reduced states of the channel. Analysis of the open and closed time distributions showed that DTNB had no effect on open and closed time distributions shorter than 4 ms. On the other hand, DTNB decreased the life time of bursts and increased the interburst interval. N-ethylmaleimide (NEM), a substance that reacts with thiol groups of cystein residues in proteins, induced irreversible closure of the channel. The thiol oxidizing agents (DTNB, NEM) inhibited of the $K_{ATP}$ channel only, when added to the cytoplasmic side. The results suggested that metabolism-induced changes in the thiol redox can also modulate $K_{ATP}$ channel activity and that a modulatory site of thiol redox may be located on the cytoplasmic side of the $K_{ATP}$ channel in rabbit ventricular myocytes.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.3
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• pp.97-106
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• 2007

The present study was attempted to investigate the effect of nicorandil, which is an ATP-sensitive potassium ($K_{ATP}$) channel opener, on secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane depolarization from the isolated perfused rat adrenal glands. The perfusion of nicorandil ($0.3{\sim}3.0mM$) into an adrenal vein for 90 min produced relatively dose-and time-dependent inhibition in CA secretion evoked by ACh (5.32 mM), high $k^+$ (a direct membrane depolarizer, 56 mM), DMPP (a selective neuronal nicotinic receptor agonist, $100{\mu}M$ for 2 min), McN-A-343 (a selective muscarinic $M_1$ receptor agonist, $100{\mu}M$ for 4 min), Bay-K-8644 (an activator of L-type dihydropyridine $Ca^{2+}$ channels, $10{\mu}M$ for 4 min) and cyclopiazonic acid (an activator of cytoplasmic $Ca^{2+}$-ATPase, $10{\mu}M$ for 4 min). In adrenal glands simultaneously preloaded with nicorandil (1.0 mM) and glibenclamide (a nonspecific $K_{ATP}$-channel blocker, 1.0 mM), the CA secretory responses evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were recovered to the considerable extent of the control release in comparison with that of nicorandil-treatment only. Taken together, the present study demonstrates that nicorandil inhibits the adrenal CA secretion in response to stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as by membrane depolarization from the isolated perfused rat adrenal glands. It seems that this inhibitory effect of nicorandil may be mediated by inhibiting both $Ca^{2+}$ influx and the $Ca^{2+}$ release from intracellular store through activation of $K_{ATP}$ channels in the rat adrenomedullary chromaffin cells. These results suggest that nicorandil-sensitive $K_{ATP}$ channels may play an inhibitory role in the regulation of the rat adrenomedullary CA secretion.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.4
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• pp.189-194
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• 2011

ATP-sensitive $K^+$ channels ($K_{ATP}$) are major component of preventing ischemia-reperfusion injury. However, there is little information regarding to the expressional difference of $K_{ATP}$ and its function between left and right ventricles. In this study, we measured the lactate dehydrogenase release of rabbit heart slices in vitro and determined the difference of the $K_{ATP}$ expression at the both ventricles by measuring the level of $K_{ATP}$-forming Kir6.2 (OcKir6.2) mRNA using in situ hybridization. The hearts were preconditioned with 15 min hypoxia and reoxygenated for 15 min before a hypoxic period of 60 min, followed by reoxygenation for 180 min. With hypoxic preconditioning (100% $N_2$) with 15 min, left ventricles (LV) showed higher release of LDH comparing with right ventricles (RV). Adding $K_{ATP}$ blocker glibenclamide ($10{\mu}M$) prior to a hypoxic period of 60 min, hypoxic preconditioning effect of RV was more abolished than LV. With in situ hybridization, the optical density of OcKir6.2 was higher in RV. Therefore, we suggest that different $K_{ATP}$ expression between LV and RV is responsible for the different response to hypoxia and hypoxic preconditioning of rabbit hearts.

• Proceedings of the Ginseng society Conference
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• 2006.05a
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• pp.69-70
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• 2006

Purpose: Panaxadiols are more potent than panaxatriols as far as insulin secretory activity is concerned. In this study, we examined insulin secretory activity and mechanism of compound K (CK), a major intestinal bacterial metabolite of ginsenosides. Method: Insulin secretory activity of CK was examined using pancreatic beta cells and in Oral Glucose Tolerance Test assay. In addition, insulin secretory mechanism was studied in terms of calcium dependent or independent pathways. Results: In vitro, CK enhanced the insulin secretion concentration-dependently when compared to glucose-stimulated control cells. Insulin secretory mechanism of CK seems to block ATP sensitive K channels, which was confirmed by diazoxide (K channel opener) but, insulin resistance ameliorating activity of CK can't be ruled out. In vivo, CK showed hypoglycemic effect in OGTT.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.6
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• pp.341-348
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• 2003

Mechanical stimuli to the cardiac myocytes initiate many biochemical and physiological events. Stretch-activated cation channels have been suggested to mediate these events. In this study, cell-attached and inside-out excised-patch clamp methods were used to identify stretch-activated cation channels in adult rat atrial myocytes. Channel openings were increased in cell-attached configuration when negative pressure was applied to the pipette, and also in inside-out excised patches by negative pressure. The channel was not permeable to $Cl^-$, $Na^+$ and $Cs^+$, but selectively permeable to $K^+$, and the degree of activation was dependent on the magnitude of negative pressure (full activation at ${\sim} -50 mmHg). In symmetrical 140 mM KCl, the slope conductance was $51.2{\pm}3$ pS between the potentials of -80 and 0 mV and $55{\pm}6$ pS between 0 and +80 mV (n=5). Glibenclamide ($100{mu}M$) or ATP (2 mM) failed to block the channel openings, indicating that it is not ATP-sensitive $K^+$ channel. Arachidonic acid ($30{mu}M$), which has been shown to activate a $K^+$ channel cooperatively with membrane stretch, did not affect the channel activity. $GdCl_3$ ($100{mu}M$) also did not alter the activity. These results demonstrate that the mechanical stretch in rat atrial myocytes activates a novel $K^+$-selective cation channel, which is not associated with other $K^+$ channels such as ATP-sensitive and arachidonic acid-activated $K^+$ channel.

• Journal of Ginseng Research
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• v.23 no.4
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• pp.235-238
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• 1999

ATP-sensitive $K^+$ channels $(K_{ATP})$ are expressed in vascular smooth muscle cells, skeletal muscle cells, pancreatic ${\beta}$ cells, neurons and epithelial cells. $K_{ATP}$ contributes to regulate membrane potential to control vascular tone, to protect myocardial ischemia, and to regulate insulin secretion in pancreatic ${\beta}$ cells. We previously demonstrated that ginseng saponins and ginsenoside $Rg_3$ activated maxi $Ca^{2+}-activated\;K^+$ channel, and this might cause vasodilation. Because $K_{ATP}$ plays an important roles to regulate the resting membrane potential in vascular smooth muscle cells, we investigated whether ginsenoside $Rg_3$ produces vasodilation by activating $K_{ATP}$ We showed in this study that $K_{ATP}$ is expressed in rabbit coronary artery smooth muscle cells. $K_{ATP}$ was inwardly rectifying and was inhibited by intemal application of ATP. Micromolar minoxidil activated, but glyburide inhibited the activity of $K_{ATP}$ Ginsenoside $Rg_3$ relieved inactivaiton of whole-cell $K_{ATP}$ current without affecting the peak amplitude of $K_{ATP}$ currents presumably due to more opening of the channels.

• Korean Journal of Veterinary Research
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• v.35 no.2
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• pp.245-254
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• 1995

The density of ATP-sensitive potassium($K_{APT}$) channels, that open as intracellular ATP concentration falls below a critical level, is very high in skeletal muscle surface membrane and those high density may imply that $K_{ATP}$ channels have very important physiological roles. To elucidate a role of $K_{ATP}$ in relation to fatigue, the modulating effects of potassium channel openers and blockers on the fatigue velocity(FV) of mouse extensor hallucis longus muscle(EHL) were investigated in vitro. Twitch contraction was induced by an electrical field stimulation (EFS: 24-48V, 20ms, 0.2-4Hz) and resulting contraction force was isometrically recorded. The twitch forces were gradually decreased to 25% of initial contraction force(ICF) in $37.52{\pm}1.55sec$($mean{\pm}s.e.m.$, n=135), indicating the fatigue phenomena. The mean velocity for development of the fatigue was measured during the period that twitch force decreased to half($FV_{0/0.5}$) and during the period from half to 25%($FV_{0.5/0.25}$) of ICF. The fatigue was induced once every one hour and the tissue response was stable for up to 4 hours. In control condition, ICF was $5.8{\pm}0.12g$ (n=144) and decreased to 50% of ICF with the mean fatigue velocity of $0.182{\pm}0.006g/sec$($FV_{0/0.5}$, n=135) and from 50% to 25% of ICF with $0.084{\pm}0.004g/sec$($FV_{0.5/0.25}$, n=135). Cromakalim($50{\mu}M$) significantly increased $FV_{0.5/0.25}$(n=4). Glibenclamide($IC_{50}>50{\mu}M$), $Ba^{2+}$($IC_{50}=10{\mu}M$), 4-aminopyridine($FV_{0/0.5}$, $IC_{50}=0.5mM$; $FV_{0.5/0.25}$, $IC_{50}=2mM$) decreased both $FV_{0/0.5}$ and $FV_{0.5/0.25}$ concentration-dependently up to 75%. $TEA^+$(30mM), E-4031($10{\mu}M$), tolbutamide(1mM) decreased $FV_{0.5/0.25}$, but apamin(300nM) and $TEA^+$(10mM) showed no significant effects. Our results suggest that activation of the $K_{ATP}$ channels may be major cause of $K^+$ outflux during development of the fatigue and the isolated EHL muscle could be an useful experimental preparation in studying the fatigue phenomena in skeletal muscle. In addition, the possibility of activation of delayed rectifier during the fatigue development remains to be studied further.