• The Korean Journal of Physiology and Pharmacology
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• v.2 no.2
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• pp.225-232
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• 1998

To investigate the possible involvement of outward potassium ($K^+$) currents in nitric oxide-induced relaxation in intestinal smooth muscle, we used whole-cell patch clamp technique in freshly dispersed guinea-pig ileum longitudinal smooth muscle cells. When cells were held at -60 mV and depolarized from -40 mV to -50 mV in 10 mV increments, sustained outward $K^+$ currents were evoked. The outward $K^+$ currents were markedly increased by the addition of 10 ${\mu}M$ sodium nitroprusside (SNP). 10 ${\mu}M$ S-nitroso-N-acetylpenicillamine (SNAP) and 1 mM 8-Bromo-cyclic GMP (8-Br-cGMP) also showed a similar effect to that of SNP. 1 mM tetraethylammonium (TEA) significantly reduced depolarization-activated outward $K^+$ currents. SNP-enhanced outward $K^+$ currents were blocked by the application of TEA. High EGTA containing pipette solution (10 mM) reduced the control currents and also inhibited the SNP-enhanced outward $K^+$ currents. 5 mM 4-aminopyridine (4-AP) significantly reduced the control currents but showed no effect on SNP-enhanced outward $K^+$ currents. 0.3 ${\mu}M$ apamin and 10 ${\mu}M$ glibenclamide showed no effect on SNP-enhanced outward $K^+$ currents. 10 ${\mu}M$ 1H-[1,2,4]oxadiazolo [4,3-a]quinoxaline-1-one (ODQ), a specific inhibitor of soluble guanylate cyclase, significantly blocked SNP-enhanced $K^+$ currents. We conclude that NO donors activate the $Ca^{2+}-activated$ $K^+$ channels in guinea-pig ileal smooth muscle via activation of guanylate cyclase.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.3
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• pp.143-147
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• 2002

Granule cells in dentate gyrus of hippocampus relay information from entorhinal cortex via perforant fiber to pyramidal cells in CA3 region. Their electrical activities are known to be closely associated with seizure activity as well as memory acquisition. Since action potential is a stereotypic phenomena which is based on all-or-none principle of $Na^+$ current, the neuronal firing pattern is mostly dependent on afterpotentials which follows the stereotypic $Na^+$ spike. Granule cells in dentate gyrus show afterdepolarization (ADP), while interneurons in dentate gyrus have afterhyperpolarizaton. In the present study, we investigated the ionic mechanism of afterdepolarization in hippocampal dentate granule cell. Action potential of dentate granule cells showed afterdepolarization, which was characterized by a sharp notch followed by a depolarizing hump starting at about $-49.04{\pm}1.69\;mV\;(n=43,\;mean{\pm}SD)$ and lasting $3{\sim}7$ ms. Increase of extracellular $Ca^{2+}$ from 2 mM to 10 mM significantly enhanced the ADP both in amplitude and in duration. A $K^+$ channel blocker, 4-aminopyridine (4-AP, 2 mM), enhanced the ADP and often induced burst firings. These effects of 10 mM $Ca^{2+}$ and 4-AP were additive. On the contrary, the ADP was significantly suppressed by removal of external $Ca^{2+},$ even in the presence of 4-AP (2 mM). A $Na^+$ channel blocker, TTX (100 nM), did not affect the ADP. From these results, it is concluded that the extracellular $Ca^{2+}$ influx contributes to the generation of ADP in granule cells.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.2
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• pp.169-183
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• 1997

We have investigated the two types of voltage-dependent outward potassium (K) currents, i.e. delayed rectifier K current ($I_{K(V)}$) and 'A-like' transient outward K current ($I_{to}$) with patch-clamp technique in single smooth muscle cells (SMCs) isolated from rabbit basilar artery, and investigated the characteristics of them. The time-courses of activation were well fitted by exponential function raised to second power ($n^2$) in $I_{K(V)}$ and fourth power ($n^4$) in $I_{to}$. The activation, inactivation and recovery time courses of $I_{to}$ were much faster than that of $I_{K(V)}$. The steady-state activation and inactivation of $I_{K(V)}$ was at the more hyperpolarized range than that of $I_{to}$ contrary to the reports in other vascular SMCs. Tetraethylammonium chloride (TEA; 10 mM) markedly inhibited $I_{K(V)}$ but little affected $I_{to}$. 4-Aminopyridine (4-AP) had similar inhibitory potency on both currents. While a low concentration of $Cd^{2+}$ (0.5 mM) shifted the current- voltage relationship of $I_{to}$ to the positive direction without change of maximum conductance, $Cd^{2+}$ did not cause any appreciable change for $I_{K(V)}$.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.5
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• pp.463-468
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• 2013

Acute hypoxia induces contraction of pulmonary artery (PA) to protect ventilation/perfusion mismatch in lungs. As for the cellular mechanism of hypoxic pulmonary vasoconstriction (HPV), hypoxic inhibition of voltage-gated $K^+$ channel (Kv) in PA smooth muscle cell (PASMC) has been suggested. In addition, our recent study showed that thromboxane $A_2$ ($TXA_2$) and hypoxia-activated nonselective cation channel ($I_{NSC}$) is also essential for HPV. However, it is not well understood whether HPV is maintained in the animals exposed to ambient hypoxia for two days (2d-H). Specifically, the associated electrophysiological changes in PASMCs have not been studied. Here we investigate the effects of 2d-H on HPV in isolated ventilated/perfused lungs (V/P lungs) from rats. HPV was almost abolished without structural remodeling of PA in 2d-H rats, and the lost HPV was not recovered by Kv inhibitor, 4-aminopyridine. Patch clamp study showed that the hypoxic inhibition of Kv current in PASMC was similar between 2d-H and control. In contrast, hypoxia and $TXA_2$-activated $I_{NSC}$ was not observed in PASMCs of 2d-H. From above results, it is suggested that the decreased $I_{NSC}$ might be the primary functional cause of HPV disappearance in the relatively early period (2 d) of hypoxia.

• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.99-108
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• 1991

The effect of racemic Ketamine HCl was observed on excitable membranes of sciatic nerve fibres and toe muscles from frog. Ketamine significantly depressed the amplitude of the action potential, maximum rate of rise and that of fall of action potentials of sciatic nerve by dose-dependent and time-course manner, and also it produced the inhibition of $K^+-contracture$ in toe muscle. We used two different ways of sucrose gap method to to obtain the better results from sciatic nerve. We observed and compared the effect of ketamine on sciatic nerve with naloxone, 4-AP (4-aminopyridine) and TEA (Tetraethylammonium). Naloxone significantly but not totally blocked the effect of ketamine both on nerve and on skeletal muscle. 4-AP or TEA by itself had a significant depressant effect on the action potentials on nerve by central perfusion (extracellular perfusion), but both of these drugs did not much affect the action of Ketamine on nerve. The reversibility of effect of Ketamine (10 mM) was observed both on nerve and on skeletal muscles when exposed to drug for short duration. The effects of racemic ketamine described may provide to support that one of the mechanisms of the action of Ketamine on nerve and on muscles of frog might be related to non-specifically effect on receptors within the ion channels $(K^+-channel,\;Na^+-channel\;or\;slow\;Ca^{++}\;channel)$ at higher dose which produces anesthetic effect and also it interacts specifically with one of the opioid receptors or subtype of these receptors which is sensitive to Naloxone at lower dose which produces analgesia.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.4
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• pp.131-135
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• 2008

The profile of membrane currents was investigated in differentiated neuronal cells derived from human neural stem cells (hNSCs) that were obtained from aborted fetal cortex. Whole-cell voltage clamp recording revealed at least 4 different currents: a tetrodotoxin (TTX)-sensitive $Na^+$ current, a hyperpolarization-activated inward current, and A-type and delayed rectifier-type $K^+$ outward currents. Both types of $K^+$ outward currents were blocked by either 5 mM tetraethylammonium (TEA) or 5 mM 4-aminopyridine (4-AP). The hyperpolarization-activated current resembled the classical $K^+$ inward current in that it exhibited a voltage-dependent block in the presence of external $Ba^{2+}$ (30 ${\mu}$M) or $Cs^+$ (3${\mu}$M). However, the reversal potentials did not match well with the predicted $K^+$ equilibrium potentials, suggesting that it was not a classical $K^+$ inward rectifier current. The other $Na^+$ inward current resembled the classical $Na^+$ current observed in pharmacological studies. The expression of these channels may contribute to generation and repolarization of action potential and might be regarded as functional markers for hNSCs-derived neurons.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.2
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• pp.73-77
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• 2008

Recent studies have documented that testosterone relaxes several smooth muscles by modulating $K^+$ channel activities. Smooth muscles of seminal vesicles playa fundamental role in ejaculation, which might involve testosterone. This study was aimed to assess the role of testosterone in seminal vesicular motility by studying its effects on contractile agents and on the ion channels of single vesicular myocytes in a rabbit model. The contractile responses of circular smooth muscle strips of rabbit seminal vesicles to norepinephrine ($10{\mu}M$), a high concentration of KCI (70 mM), and testosterone ($10{\mu}M$) were observed. Single vesicular myocytes of rabbit were isolated using proteolytic enzymes including collagenase and papain. Inside-out, attached, and whole-cell configurations were examined using the patch clamp technique. The applications of $10{\mu}M$ norepinephrine or 70 mM KCl induced tonic contractions, and $10{\mu}M$ testosterone (pharmacological concentration) evoked dose-dependent relaxations of these precontracted strips. Various $K^+$ channel blockers, such as tetraethylammonium (TEA; $10{\mu}M$), iberiotoxin ($0.1{\mu}M$), 4-aminopyridine (4-AP, $10{\mu}M$), or glibenclamide ($10{\mu}M$) rarely affected these relaxations. Single channel data (of inside-out and attached configurations) of BK channel activity were also hardly affected by testosterone ($10{\mu}M$). On the other hand, however, testosterone reduced L-type $Ca^{2+}$ currents significantly, and found to induce acute relaxation of seminal vesicular smooth muscle and this was mediated, at least in part, by $Ca^{2+}$ current inhibition in rabbit.

• Journal of the Korean Chemical Society
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• v.30 no.2
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• pp.145-151
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• 1986

Using a new conductometric method, dissociation constants of 3-cyano, 4-cyano, 3-amino and 4-aminopyridine were measured in the temperature range 15 ∼ 40${\circ}C$ and pressure up to 2500bar in aqueous media. This method is convenient to apply to the low dissociative acid and base but have to do tedious extrapolating procedure for the ionic conductance in elaborated temperatures and pressures and have to know any reference dissociation constant. The measured dissociation constants were increased as the temperature increase but decreased as the pressure increase. From the constants, various thermodynamic properties were evaluated and discussed for the dissociation reactions.

• Journal of Veterinary Clinics
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• v.7 no.2
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• pp.501-509
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• 1990

This study was designed to examine effects of $\alpha$$_2$-Adrenergic Antagonists on blood chemical values in xylazine-sedated dogs. Twenty-four crossbred dogs of both sexes were intramusculary injected with a standard dosage of xylazine(2.2mg/kg of body weight). Righting reflex was uniformly lost and considered to be the point of maximum sedation. When the dogs were maximally sedated, tested groups were in-travenously injected with yohimbine 0.125mg/kg, 4-aminopyridine(4-AP) 0.3mg/kg, and a combination of yohimbine with 4-AP. Control group was intravenously 1 $m\ell$ of physiological saline solution. Total protein(T.P), albumin, glucose, aspartate aminotransferase(AST), alanine aminotrnasferase(ALT), blood urea nitrogen(BUN) were analyzed in the conditions of 0-, 30-, 60- and 120-minute after the administration of drugs. The results obtained in the study were as follows. 1. Changes of T.P, albumin, AST, ALT and BUN values in the control group were not significant during or after xylazine administration for at least 120minutes. 2. No changes of T.P, albumin, AST, ALT and BUN values in the tested groups were observed during or after $\alpha$$_2$-Adrenergic Antagonists treatment. 3. Serum glucose values of control group were getting remarkably increased after xylazine injection. 4. The xylasine-induced hyperglycemia was reversed in the dogs administrated with $\alpha$$_2$-Adrenergic Antagonists. Therefore, the results of the study show that the combined treatment with antagonists may be useful for accidental overdoses of xylazine and rapid reversal of animals sedated with xylazine.

• The Korean Journal of Physiology
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• v.26 no.1
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• pp.27-35
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• 1992

We used the whole cell patch clamp technique to examine the ionic basis for the tail current after depolarizing pulse in single atrial myocytes of the rabbit. We recorded the tail currents during various repolarizations after short depolarizing pulse from a holding potential of -70 mV. The potassium currents were blocked by external 4-aminopyridine and replacement of internal potassium with cesium. The current was reversed to the outward direction above +10 mV. High concentrations of intracellular calcium buffer inhibited the activation of the current. Diltiazem and ryanodine blocked it too. These data suggest that the current is activated by intracellular calcium released from sarcoplasmic reticulumn. When the internal chloride concentration was increased, the inward tail current was increased. The current was partially blocked by the anion transport blocker niflumic acid. The current voltage curve of the niflumic acid sensitive current component shows outward rectification and is well fitted to the current voltage curve of the theoretically predicted chloride current calculated from the constant field equation. The currents recorded in rabbit atrial myocytes, with the method showing isolated outward Na Ca exchange current in ventricular cells of the guinea pig, suggested that chloride conductance could be activated with the activation of Na/ca exchange current. From the above results it is concluded that a chloride sensitive component which is activated by intracellular calcium contributes to tail currents in rabbit atrial cells.