BACKGROUND: This study investigated the effects of the K+ channel opener, pinacidil on hypoxic pulmonary vasoconstriction in isolated perfused rabbit lungs. In order to evaluate the vasodilatation mechanism of K+ channel opener, we also studied the effects of two K+ channel blocker, tetraethylammonium (TEA), a Ca2+ activated K+ channel blocker and glibenclamide (GLB), an ATP-sensitive K+ channel blocker. METHODS: Isolated lungs from white rabbits were ventilated with a normoxic gas (21%O2-5%CO2-74%N2) and a hypoxic gas (3%O2- 5%CO2-92%N2) alternatively, and then perfused with blood-containing perfusate solution. After a hypoxic pressor response (HPR) had been obtained, various drugs were added to the perfusate reservoir to achieve the predetermined circulating concentration, and the influences of the drugs on HPR were then tested. RESULTS: Pinacidil (0.3-6.0 mcM) produced a dose-dependent pulmonary vasodilation on hypoxic ventilation challenge. TEA (1 mM) caused pulmonary vasoconstriction in normoxic ventilation and potentiated a hypoxic pressor response. When the hypoxic pressor response was potentiated by TEA, pinacidil (1.0, 3.0 mcM) reduced the contraction, but GLB did not cause pulmonary vasoconstriction under normoxic ventilation, potentiate a hypoxic pressor response. CONCLUSIONS: Piacidil is capable of opposing the pulmonary responses of acute hypoxia. Moreover the effects of TEA and GLB suggest that HPV might be mediated through Ca2+ activated K+ channels, not through ATP-sensitive K+ channels.
Anoxia ; Glyburide* ; Lung* ; Pinacidil* ; Potassium Channels, Calcium-Activated ; Rabbits ; Tea ; Tetraethylammonium ; Vasoconstriction* ; Vasodilation ; Ventilation

BACKGROUND: Recently, the phannacologic and therapeutic significance of various types of potassium channels are being realized. Thus it was attempted to delineate the role of voltage-gated K+ -channels on the excitation-contraction coupling in skeletal muscle. METHODS: The effects of tetraethylammonium, a well known K+ -channel blocker, on the electrically-evoked twitch response, train-of-four and tetanic stimulation, and the influence of various agents on the these effects were studied in the isolated rat hemi-diaphragm preparation. RESULTS: Tetraethylammonium (1 & 3 mM) increased the electrically-evoked twitch response, but the large dose (10 mM) decreased the twitch response. And tetraethylammonium decreased the TOF- and tetanus-ratio in a dose-related fashion. d-Tubocurarine(1 microM) decreased the twitch response, and tetraethylammonium recovered the d-tubocurarine-induced-depression of twitch response. When the Ca++(6x) and K+ (2x) concentration of the medium were increased, the twitch response caused by tetraethylammonium were slightly inhibited than that observed in the normal solution, but the fade phenomenon was potentiated. The tetraethylammonium (10 mM)-induced depression of twitch response were reduced by reducing the stimulus frequency to 0.01 Hz and choline (400 microM) treatment. And N-ethylmaleimide inhibited the tetraethylammonium-induced increment of twitch response and also potentiated the tetraethylammonium-induced fade phenomenon. However, it is noteworth the 4-aminopy- ridine, another K+ -channel bloker, potentiated the electrically-evoked twitch response but did not affect the TOF-and tetanusratio. CONCLUSION: These result indicate that tetraethylammonium elicited two districtive types of response in the rat phrenic-hemidiaphragm preparation. The potentiating effects of twitch response is mediated by blocking delayed K+ -rectifier channel and decreasing effects of twitch response, TOF-and tetanus-ratio is may be due to decreased the acetylcholine release from presynaptic nerve terminal.
Acetylcholine ; Animals ; Choline ; Depression ; Ethylmaleimide ; Muscle, Skeletal ; Potassium Channels ; Rats* ; Tetraethylammonium*

Potassium channel blockers slow depolarization, broaden the action potential, and thus pro- mote the open and inactivated Na+ channel states. The ability of local anesthetics to reduce the amplitude of compound action potential(CAP) of rat sciatic nerve was examined in the presence and absence of teteraethylammonium chloride(TEA) that selectively block K+ channels, In the presence of 1.3X10-5 M bupivacaine that inhibit the CAP by 22.5% at tonic stimulation, the addition of TEA(10-1M) increased this inhibition by another 27.5% and increased another 50% by phasic stimulation(20Hz). Also, dose response curve of bupivacaine in the presence of TEA(10-1M) showed marked shift to left of curve. The re- covery kinetics of bupivacaine in the presence of various coneentration of TEA(10-2-10-1M) showed marked delay of recovery(2X10-2 M), reocurrence of inhibition(90min,5X10-2 M), even no recovery(10-1M). TEA alone slightly depolarized the resting membrane which was represented as increment of CAP height from 0.9%(3min) to 12.3%(80min), and broadened mid-peak amplitude width by 2 times in 5X10-1M, 5.3 times in 1M. These experiments directly demonstrated that TEA potentiated the inhibition of CAP by bupivacaine and showed the poesibility of mixture of TEA and local anesthetics to potenti- ate impulse conduction blockade.
Action Potentials ; Anesthetics, Local ; Animals ; Bupivacaine* ; Kinetics ; Membranes ; Potassium Channel Blockers ; Rats ; Sciatic Nerve ; Tea ; Tetraethylammonium*

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 Ba2+ (30micrometer) or Cs+ (3micrometer). 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.
4-Aminopyridine ; Action Potentials ; Humans ; Membranes ; Neural Stem Cells ; Neurons ; Tetraethylammonium ; Tetrodotoxin

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 1-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).
4-Aminopyridine ; Basilar Artery* ; Muscle, Smooth* ; Myocytes, Smooth Muscle* ; Patch-Clamp Techniques ; Potassium* ; Tetraethylammonium

PURPOSE: The goal of this study was to investigate the effect of tetraethylammonium (TEA) on the excitability of visual cortex, and observe the induction of epileptiform activity. Also, it was aimed to define the characteristics of spontaneous activity and observe the effect of GABAA antagonist, NMDA antagonist and non-NMDA antagonist on the TEA-induced epileptiform activity. METHODS: The visual cortex slices in this study were obtained from 19 to 23 day-old Sprague-Dawley rats. Extracellular cellular recording was performed to observe the induction of epileptiform discharge perfused by artificial CSF containing 1, 5 and 10 mM TEA and the effect of 10 ?M 6-cyano-7-nitroquinoxaline-dione disodium(CNQX) and 50 microM D-(-)-2-amino-5-phosphonopentanoic acid(D-AP5) on the 10 mM TEA-induced epileptiform activity. RESULTS: Spontaneous epileptiform activities were observed in 5 and 10 mM TEA groups. The addition of 5 ?M BIC blocked the TEA-induced spontaneous ictal epileptiform activity but didn't block the TEA-induced spontaneous interictal epileptiform activity. The addition of 10 ?M CNQX shortened duration, decreased frequency and amplitude of the TEA-induced spontaneous epileptiform activity. The addition of 50 microM D-AP5 blocked the TEA-induced spontaneous ictal and interictal epileptiform activity. CONCLUSION: TEA induced the increased excitability in the visual cortex and spontaneous epileptiform activity. 5 ?M BIC blocked the TEA-induced spontaneous ictal epileptiform activity and GABAA antagonist BIC plays a role in limiting the epileptiform discharge. The TEA-induced spontaneous epileptiform activity induction was decreased by CNQX and blocked by D-AP5. NMDA and non-NMDA are required to modify the TEA-induced spontaneous epileptiform activity.
6-Cyano-7-nitroquinoxaline-2,3-dione ; Animals ; GABA Antagonists ; N-Methylaspartate ; Rats* ; Rats, Sprague-Dawley ; Tea ; Tetraethylammonium ; Visual Cortex*

BACKGROUND: An increase of the extracellular K+concentrations up to about 8 mM in the isolated vessels causes relaxation in pre-contracted state. In order to elucidate the mechanisms of K+induced relaxation and compare with that of 2-kidney, 1 clip (2K1C) renal hypertensive rats, we recorded aortic vascular tension using an organ bath study. METHOD: 2K1C hypertension was made by clipping the left renal artery and age-matched control rats received a sham treatment. Thoracic aortic rings were mounted in tissue baths for measurement of isometric contractile force. RESULTS: Exposure to K+(from 2 to 8 mM) relaxed a phenylephrine (2 x 10-6 M)-induced contraction in K+free Krebs-Ringer solution, dose-dependently. Ouabain (10-5 M) enhanced the K+induced relaxation in above 2 mM K+ The K+induced relaxation was still induced in endothelium-denuded condition. Incubation with the K+channel blockers such as tetraethylammonium (TEA, 1 mM), glibenclamide (10-5 M), 4-aminopyridine (3 mM), barium (5 mM) and cesium (2 mM) did not affect on the K+induced relaxation. In renal hypertensive rats, the K+induced relaxation was markedly suppressed and ouabain enhanced it. CONCLUSIONS: These results suggest that the K+induced relaxation in aorta be mediated by Na-pump independent mechanisms, and the decrease of the K+induced relaxation in the renal hypertensive rats may be a possible mechanism of hypertension.
4-Aminopyridine ; Animals ; Aorta ; Barium ; Baths ; Cesium ; Glyburide ; Hypertension ; Muscle, Smooth* ; Ouabain ; Phenylephrine ; Placebos ; Rats* ; Relaxation ; Renal Artery ; Tetraethylammonium ; Vasodilation*

BACKGROUND: An increase of the extracellular K+concentrations up to about 8 mM in the isolated vessels causes relaxation in pre-contracted state. In order to elucidate the mechanisms of K+induced relaxation and compare with that of 2-kidney, 1 clip (2K1C) renal hypertensive rats, we recorded aortic vascular tension using an organ bath study. METHOD: 2K1C hypertension was made by clipping the left renal artery and age-matched control rats received a sham treatment. Thoracic aortic rings were mounted in tissue baths for measurement of isometric contractile force. RESULTS: Exposure to K+(from 2 to 8 mM) relaxed a phenylephrine (2 x 10-6 M)-induced contraction in K+free Krebs-Ringer solution, dose-dependently. Ouabain (10-5 M) enhanced the K+induced relaxation in above 2 mM K+ The K+induced relaxation was still induced in endothelium-denuded condition. Incubation with the K+channel blockers such as tetraethylammonium (TEA, 1 mM), glibenclamide (10-5 M), 4-aminopyridine (3 mM), barium (5 mM) and cesium (2 mM) did not affect on the K+induced relaxation. In renal hypertensive rats, the K+induced relaxation was markedly suppressed and ouabain enhanced it. CONCLUSIONS: These results suggest that the K+induced relaxation in aorta be mediated by Na-pump independent mechanisms, and the decrease of the K+induced relaxation in the renal hypertensive rats may be a possible mechanism of hypertension.
4-Aminopyridine ; Animals ; Aorta ; Barium ; Baths ; Cesium ; Glyburide ; Hypertension ; Muscle, Smooth* ; Ouabain ; Phenylephrine ; Placebos ; Rats* ; Relaxation ; Renal Artery ; Tetraethylammonium ; Vasodilation*

PURPOSE: Intracavernous injection of PGE1 or papaverine is widely used in the diagnosis and treatment of erectile dysfunction. However, these drugs have several side effects such as pain, priapism, and fibrotic lesions. In this study, we assessed the effects of pinacidil (a K+ -ATP - channel opener) as an alternative for inducing penile erection. METHODS: Using a feline model, the magnitude of penile erection caused by pinacicil was compared with that caused by other drugs, namely acetylcholine, PGE1 and L-arginine. The effects of K+ -channel blockers(4-aminopyridine, glibenclamide, and tetraethylammonium; TEA) and pinacidil on the induced erections were investigated. RESULTS: Intra-arterial injection of pinacicil increased the intracavernous pressure (ICP) in a dose-dependent fashion, and the increase in ICP induced by pinacicil plus acetylcholine, PGE1 or L-arginine was more pronounced than that induced by any of these drugs alone. Furthermore, pinacicil (10(-3)M/mL) effectively reversed the inhibitory effects of the K+-channel blockers on cavernous relaxation induced by acetylcholine, PGE1 or L-arginine (P<0.01). Notably, pinacidil induced cavernous relaxation even in cases refractory to a higher concentration <10(-1) M/mL) of erectics (n = 11; p<0.01). CONCLUSIONS: These results suggest that pinacidil is effective in relaxing feline erectile tissue in vivo, probably via increased K+ permeability and subsequent hyperpolarization. Further comparative studies with human erectile tissue and clinical testing are required to show whether K+-channel openers can be used in the diagnosis and treatment of erectile dysfunction.
Acetylcholine ; Alprostadil ; Arginine ; Diagnosis ; Erectile Dysfunction* ; Glyburide ; Humans ; Injections, Intra-Arterial ; Male ; Papaverine ; Penile Erection ; Permeability ; Pinacidil ; Priapism ; Relaxation ; Tetraethylammonium

PURPOSE: Intracavernous injection of PGE1 or papaverine is widely used in the diagnosis and treatment of erectile dysfunction. However, these drugs have several side effects such as pain, priapism, and fibrotic lesions. In this study, we assessed the effects of pinacidil (a K+ -ATP - channel opener) as an alternative for inducing penile erection. METHODS: Using a feline model, the magnitude of penile erection caused by pinacicil was compared with that caused by other drugs, namely acetylcholine, PGE1 and L-arginine. The effects of K+ -channel blockers(4-aminopyridine, glibenclamide, and tetraethylammonium; TEA) and pinacidil on the induced erections were investigated. RESULTS: Intra-arterial injection of pinacicil increased the intracavernous pressure (ICP) in a dose-dependent fashion, and the increase in ICP induced by pinacicil plus acetylcholine, PGE1 or L-arginine was more pronounced than that induced by any of these drugs alone. Furthermore, pinacicil (10(-3)M/mL) effectively reversed the inhibitory effects of the K+-channel blockers on cavernous relaxation induced by acetylcholine, PGE1 or L-arginine (P<0.01). Notably, pinacidil induced cavernous relaxation even in cases refractory to a higher concentration <10(-1) M/mL) of erectics (n = 11; p<0.01). CONCLUSIONS: These results suggest that pinacidil is effective in relaxing feline erectile tissue in vivo, probably via increased K+ permeability and subsequent hyperpolarization. Further comparative studies with human erectile tissue and clinical testing are required to show whether K+-channel openers can be used in the diagnosis and treatment of erectile dysfunction.
Acetylcholine ; Alprostadil ; Arginine ; Diagnosis ; Erectile Dysfunction* ; Glyburide ; Humans ; Injections, Intra-Arterial ; Male ; Papaverine ; Penile Erection ; Permeability ; Pinacidil ; Priapism ; Relaxation ; Tetraethylammonium