• Molecules and Cells
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• 제25권1호
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• pp.124-130
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• 2008

Astrocyte ion channels participate in ionic homeostasis in the brain. Inward rectifying potassium channels (Kir channels) in astrocytes have been particularly implicated in $K^+$ homeostasis because of their high open probability at resting potential and their increased conductance at high concentrations of extracellular $K^+$. We examined the expression of the Kir2.1 subunit, one of the Kir channel subunits, in the mouse brain by immunohistochemistry. Kir2.1 channels were widely distributed throughout the brain, with high expression in the olfactory bulb and the cerebellum. Interestingly, they were abundantly expressed in astrocytes of the olfactory bulb, while astrocytes in other brain regions including the hippocampus did not show any detectable expression. However, Kir2.1 channel-expressing cells were dramatically increased in the hippocampus by kainic acid-induced seizure and the cells were glial fibrillary acidic protein (GFAP)-positive, which confirms that astrocytes in the hippocampus express Kir2.1 channels under pathological conditions. Our results imply that Kir2.1 channels in astrocyte may be involved in buffering $K^+$ against accumulated extracellular $K^+$ caused by neuronal hyperexcitability under phathophysiological conditions.

• The Korean Journal of Physiology and Pharmacology
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• 제5권1호
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• pp.33-40
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• 2001

The aim of present study was to define the cellular mechanisms underlying changes in delayed rectifier $K^+\;(K_{DR})$ channel function in isoproterenol-induced hypertrophy. It has been proposed that $K_{DR}$ channels play a role in regulation of vascular tone by limiting membrane depolarization in arterial smooth muscle cells. The alterations of the properties of coronary $K_{DR}$ channels have not been studied as a possible mechanism for impaired coronary reserve in cardiac hypertrophy. The present study was carried out to compare the properties of coronary $K_{DR}$ channels in normal and hypertrophied hearts. These channels were measured from rabbit coronary smooth muscle cells using a patch clamp technique. The main findings of the study are as follows: (1) the $K_{DR}$ current density was decreased without changes of the channel kinetics in isoproterenol-induced hypertrophy; (2) the sensitivity of coronary $K_{DR}$ channels to 4-AP was increased in isoproterenol-induced hypertrophy. From the above results, we suggest for the first time that the alteration of $K_{DR}$ channels may limit vasodilating responses to several stimuli and may be involved in impaired coronary reserve in isoproterenol-induced hypertrophy.

• The Korean Journal of Physiology and Pharmacology
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• 제26권4호
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• pp.277-285
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• 2022

To investigate the adverse effects of clozapine on cardiovascular ion channels, we examined the inhibitory effect of clozapine on voltage-dependent K⁺ (Kv) channels in rabbit coronary arterial smooth muscle cells. Clozapine-induced inhibition of Kv channels occurred in a concentration-dependent manner with an half-inhibitory concentration value of 7.84 ± 4.86 µM and a Hill coefficient of 0.47 ± 0.06. Clozapine did not shift the steady-state activation or inactivation curves, suggesting that it inhibited Kv channels regardless of gating properties. Application of train pulses (1 and 2 Hz) progressively augmented the clozapine-induced inhibition of Kv channels in the presence of the drug. Furthermore, the recovery time constant from inactivation was increased in the presence of clozapine, suggesting that clozapine-induced inhibition of Kv channels is use (state)-dependent. Pretreatment of a Kv1.5 subtype inhibitor decreased the Kv current amplitudes, but additional application of clozapine did not further inhibit the Kv current. Pretreatment with Kv2.1 or Kv7 subtype inhibitors partially blocked the inhibitory effect of clozapine. Based on these results, we conclude that clozapine inhibits arterial Kv channels in a concentration-and use (state)-dependent manner. Kv1.5 is the major subtype involved in clozapine-induced inhibition of Kv channels, and Kv2.1 and Kv7 subtypes are partially involved.

• The Korean Journal of Physiology and Pharmacology
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• 제7권3호
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• pp.131-142
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• 2003

We have studied mutant forms of Kir2.1 in which an aspartate residue (D172), important for gating by intracellular polyamines, is replaced by one of three basic residues (Arg, Lys or His). Such channels are highly selective for $K^+$, but show inward rectification that is a shallow function of voltage compared with that found in wild type. This inward rectification occurs with a reduced affinity for spermine and persists in the absence of polyamines. Though the unitary current-voltage relation shows some inward rectification, it is insufficient to account for that seen under whole cell recording. Channels open and shut under single channel recording, and changes of $P_{open}$ appear to generate inward rectification. In D172H, the reduction in affinity for spermine is greater when His is protonated at low $pH_i$. The effective valency for spermine is reduced from $3.09{\pm}0.07$ in wild type to $1.95{\pm}0.09$ in D172H at $pH_i$ 6.3. In the presence of dual mutants of Kir2.1, where E224 is also replaced, spermine affinity becomes undetectable. However, channels still show inward rectification and open and shut under hyper- and depolarisation, respectively. We suggest that Kir2.1 channel are able to undergo conformation changes; these changes may be important physiologically in generating inward rectification, the normal parameters of which are set by the binding of polyamines such as spermine.

• The Korean Journal of Physiology and Pharmacology
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• 제26권5호
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• pp.397-404
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• 2022

Fesoterodine, an antimuscarinic drug, is widely used to treat overactive bladder syndrome. However, there is little information about its effects on vascular K⁺ channels. In this study, voltage-dependent K⁺ (Kv) channel inhibition by fesoterodine was investigated using the patch-clamp technique in rabbit coronary artery. In whole-cell patches, the addition of fesoterodine to the bath inhibited the Kv currents in a concentration-dependent manner, with an IC₅₀ value of 3.19 ± 0.91 μM and a Hill coefficient of 0.56 ± 0.03. Although the drug did not alter the voltage-dependence of steady-state activation, it shifted the steady-state inactivation curve to a more negative potential, suggesting that fesoterodine affects the voltage-sensor of the Kv channel. Inhibition by fesoterodine was significantly enhanced by repetitive train pulses (1 or 2 Hz). Furthermore, it significantly increased the recovery time constant from inactivation, suggesting that the Kv channel inhibition by fesoterodine is use (state)-dependent. Its inhibitory effect disappeared by pretreatment with a Kv 1.5 inhibitor. However, pretreatment with Kv2.1 or Kv7 inhibitors did not affect the inhibitory effects on Kv channels. Based on these results, we conclude that fesoterodine inhibits vascular Kv channels (mainly the Kv1.5 subtype) in a concentration- and use (state)-dependent manner, independent of muscarinic receptor antagonism.

• Korean Circulation Journal
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• 제53권4호
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• pp.239-250
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• 2023

Background and Objectives: Brugada syndrome (BrS) is an inherited arrhythmia syndrome that presents as sudden cardiac death (SCD) without structural heart disease. One of the mechanisms of SCD has been suggested to be related to the uneven dispersion of transient outward potassium current (I_to) channels between the epicardium and endocardium, thus inducing ventricular tachyarrhythmia. Artemisinin is widely used as an antimalarial drug. Its antiarrhythmic effect, which includes suppression of I_to channels, has been previously reported. We investigated the effect of artemisinin on the suppression of electrocardiographic manifestations in a canine experimental model of BrS. Methods: Transmural pseudo-electrocardiograms and epicardial/endocardial transmembrane action potentials (APs) were recorded from coronary-perfused canine right ventricular wedge preparations (n=8). To mimic the BrS phenotypes, acetylcholine (3 μM), calcium channel blocker verapamil (1 μM), and I_to agonist NS5806 (6-10 μM) were used. Artemisinin (100-150 μM) was then perfused to ameliorate the ventricular tachyarrhythmia in the BrS models. Results: The provocation agents induced prominent J waves in all the models on the pseudo-electrocardiograms. The epicardial AP dome was attenuated. Ventricular tachyarrhythmia was induced in six out of 8 preparations. Artemisinin suppressed ventricular tachyarrhythmia in all 6 of these preparations and recovered the AP dome of the right ventricular epicardium in all preparations (n=8). J wave areas and epicardial notch indexes were also significantly decreased after artemisinin perfusion. Conclusions: Our findings suggest that artemisinin has an antiarrhythmic effect on wedge preparation models of BrS. It might work by inhibition of potassium channels including I_to channels, subsequently suppressing ventricular tachycardia/ventricular fibrillation.

• Journal of Photoscience
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• 제4권1호
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• pp.23-30
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• 1997

Leaf movements in nyctinastic plants are produced by changes in the turgor of extensor and flexor cells, collectively called motor cells, in opposing regions of the leaf movement organ, the pulvinus. In Samanea saman, a tropical tree of the legume family, extensor cells shrink and flexor cells swell to bend the pulvinus and fold the leaf at night, whereas extensor cells swell and flexor cells shrink to straighten the pulvinus and extend the leaf in the daytime. These changes are caused by ion fluxes primarily of potassium and chloride, across the plasma membrane of the motor cells. These ion fluxes are regulated by exogenous light signals and an endogenous biolgical clock. Inward-directed K$^+$ channels are closed in extensor and open in flexor cells in the dark period, while these channels are open in extensor and closed in flexor cells in the light period. Blue light opens the closed K$^+$ channels in extensor and closes the open them in flexor cells during darkness. Illumination of red light followed by darkness induces to open the closed K$^+$ channels in flexor and to close the open K$^+$ channels in extensor cells in the light. The dynamics of K$^+$ channels in motor cells that are controlled by light signals are consistent with the behavior of the pulvini in intact plants. Therefore, these cell types are an attractive model system to elucidate regulations of ion transports and their signal transduction pathways in plants. This review is focused on light-controlled ion movements and regulatory mechanisms involved in phosphoinositide signaling in leaf movements in nyctinastic plants.

• 대한약리학회:학술대회논문집
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• 대한약리학회 2006년도 The 6th Congress of the Federation of Asian and Oceanian Physiological Societies
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• pp.86.1-86.1
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• 2006

• 한국동물학회:학술대회논문집
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• 한국동물학회 1997년도 한국생물과학협회 학술발표대회
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• pp.194.1-194
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• 1997

No Abstract, See Full Text

• Journal of Korean Neurosurgical Society
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• 제29권6호
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• pp.719-724
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• 2000

Objectives : It has been reported that the presence of a pharmacologically inactive foreign substance, polystyrene latex bead, in subarachnoid space activates a non-specific immunological response and elicits arterial narrowing. Recently the activation of potassium($K^+$) channels may be of benefit in relieving cerebral vasospasm. The present study examined the effects of systemic administration of a ATP-sensitive $K^+$ channel activator, cromakalim, on the polystyrene latex bead-induced cerebral vasospasm. Methods : The spasm models similar to that caused by subarachnoid blood injection were created by injection of bead into rabbit cisterna magna. Intravenous injections of cromakalim were administered twice daily(bid) 30 minutes after induction of vasospasm. Animals were killed by perfusion-fixation 2 days after vasospasm. Basilar arteries were removed and sectioned, and the luminal cross-sectional areas were measured. Results : Injection of bead elicited an arterial constriction, reducing arterial diameter to 33.3% of resting tone. Cromakalim inhibited bead-induced constriction at a dose of 0.3mg/kg(Mann-Whitney test, p<0.01). Conclusion : These results support the concept that the cellular events triggered by inactivation of ATP-sensitive $K^+$ channels are responsible for the pathogenesis of vasospasm. The findings also indicate that cromakalim represents a potential therapeutic agents for the treatment of cerebral vasospasm.