TEA inhibits ACh-induced EDRF release: endothelial Ca(2+)-dependent K+ channels contribute to vascular tone

1994 ◽  
Vol 267 (3) ◽  
pp. H1135-H1141 ◽  
Author(s):  
E. Demirel ◽  
J. Rusko ◽  
R. E. Laskey ◽  
D. J. Adams ◽  
C. van Breemen
Keyword(s):  
Endothelial Cells ◽  
Patch Clamp ◽  
Outward Current ◽  
Rabbit Aorta ◽  
K Channel ◽  
Channel Blockers ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
K Channels ◽  
Donor Segment

The effects of K(+)-channel blockers on the acetylcholine (ACh)-induced relaxation of vascular smooth muscle, intracellular free Ca2+ concentration ([Ca2+]i) elevation, and ACh-evoked outward K+ current of endothelial cells of rabbit aorta were studied using bioassay, spectrofluorimetry, and patch-clamp techniques, respectively. In bioassay experiments, ACh caused relaxation of endothelium-denuded aortic rings in a concentration-dependent manner when perfused through an endothelium-intact donor segment of aorta but not when perfused directly onto the recipient aortic ring. ACh-induced relaxation was inhibited by perfusion of tetraethylammonium ions (TEA; 5 mM) through the donor but not by perfusion directly onto the recipient segment. Glibenclamide had no effect on ACh-induced relaxation of the bioassay ring in either situation. ACh increased [Ca2+]i at the endothelial surface of aortic strips but not at the adventitial surface. TEA inhibited ACh-induced [Ca2+]i elevation, whereas glibenclamide had no effect. In patch-clamp experiments with freshly isolated endothelial cells, ACh evoked a biphasic outward current which was completely abolished by TEA (3 mM). It is concluded that Ca(2+)-dependent K+ channels are important for increasing [Ca2+]i during agonist stimulation and consequently for the synthesis/release of endothelium-derived relaxing factors (EDRFs). Furthermore, endothelial ATP-sensitive K+ channels do not contribute to ACh-induced relaxation or evoke an increase in endothelial [Ca2+]i of rabbit thoracic aorta.

Metabotropic glutamate receptor agonist-induced hyperpolarizations in rat basolateral amygdala neurons: receptor characterization and ion channels

1996 ◽  
Vol 76 (5) ◽  
pp. 3059-3069 ◽  
Author(s):  
K. H. Holmes ◽  
N. B. Keele ◽  
V. L. Arvanov ◽  
P. Shinnick-Gallagher
Keyword(s):  
Dicarboxylic Acid ◽  
Glutamate Receptor ◽  
Basolateral Amygdala ◽  
Metabotropic Glutamate Receptor ◽  
Outward Current ◽  
Channel Blockers ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Metabotropic Glutamate ◽  
Outward Currents

1. Metabotropic glutamate receptor (mGluR)-agonist-induced hyperpolarizations and corresponding outward currents were analyzed in basolateral amygdala (BLA) neurons in rat brain slice preparations with current-clamp and single-electrode voltage-clamp recording to characterize the mGluR subtype(s) and the ion channel(s) mediating this response. 2. The mGluR agonist (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) induced a membrane hyperpolarization or outward current in BLA neurons in a concentration-dependent manner (median effective concentration = 34 microM; range = 10-200 microM); the 1S,3R-ACPD hyperpolarizations are recorded in 89% of neurons that accommodate or cease firing in response to a 400-ms depolarizing current injection (0.5 nA). 3. mGluR agonists elicited hyperpolarizations or outward currents in a concentration-dependent manner in the following rank order of potency: (2S,3S,4S)-alpha-(carboxycyclopropyl)glycine (L-CCG-I) > 1S,3R-ACPD > (s)-4-carboxyphenylglycine = (RS)-4-carboxy-3-hydroxyphenylglycine (4C3HPG) > L-aminophosphonobutyric acid > (1S,3S)-1-amino-cyclopentane-1,3-dicarboxylic acid. In contrast, the mGluR agonists quisqualate and ibotenate induced only depolarizations in the presence of D-2-amino-5-phosphonovalerate and 6-cyano-7-nitroquinoxaline-2,3-dione in BLA neurons. 4. The 1S,3R-ACPD-induced outward current is mediated through a large-conductance calcium-dependent potassium (BK) conductance. The BK channel blockers iberiotoxin and charybdotoxin blocked the response, as did the potassium channel blockers tetraethylammonium and 4-aminopyridine; the small-conductance calcium-activated potassium channel blocker apamin did not affect the response. 5. The mGluR-agonist-induced hyperpolarization is blocked in amygdala slices from animals pretreated with pertussis toxin (PTX). 1S,3R-ACPD hyperpolarizations were recorded in neurons contralateral but not ipsilateral to the site of PTX injection. 6. The antagonist (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG, 500 microM) reduced significantly the 1S,3R-ACPD-induced hyperpolarization. 7. In conclusion, the relative potency of L-CCG-I and 4C3HPG in evoking only hyperpolarizations (outward currents) in accommodating neurons, and the observation that MCPG (500 microM) reduces the hyperpolarization, suggest that a group-II-like mGluR underlies the hyperpolarizing response. The mGluR-induced response is sensitive to iberiotoxin and to pretreatment with PTX, suggesting activation of BK channels through a group II mGluR linked to a PTX-sensitive G protein in BLA neurons.

Ba2+, TEA+, and quinine effects on apical membrane K+ conductance and maxi K+ channels in gallbladder epithelium

1990 ◽  
Vol 259 (1) ◽  
pp. C56-C68 ◽  
Author(s):  
Y. Segal ◽  
L. Reuss
Keyword(s):  
Apical Membrane ◽  
Membrane Conductance ◽  
Membrane Resistance ◽  
K Channel ◽  
Dependent Manner ◽  
Gallbladder Epithelium ◽  
Concentration Dependent Manner ◽  
K Channels ◽  
Voltage Dependent ◽  
Channel Currents

The apical membrane of Necturus gallbladder epithelium contains a voltage-activated K+ conductance [Ga(V)]. Large-conductance (maxi) K+ channels underlie Ga(V) and account for 17% of the membrane conductance (Ga) under control conditions. We examined the Ba2+, tetraethylammonium (TEA+), and quinine sensitivities of Ga and single maxi K+ channels. Mucosal Ba2+ addition decreased resting Ga in a concentration-dependent manner (65% block at 5 mM) and decreased Ga(V) in a concentration- and voltage-dependent manner. Mucosal TEA+ addition also decreased control Ga (60% reduction at 5 mM). TEA+ block of Ga(V) was more potent and less voltage dependent that Ba2+ block. Maxi K+ channels were blocked by external Ba2+ at millimolar levels and by external TEA+ at submillimolar levels. At 0.3 mM, quinine (mucosal addition) hyperpolarized the cell membranes by 6 mV and reduced the fractional apical membrane resistance by 50%, suggesting activation of an apical membrane K+ conductance. At 1 mM, quinine both activated and blocked K(+)-conductive pathways. Quinine blocked maxi K+ channel currents at submillimolar concentrations. We conclude that 1) Ba2+ and TEA+ block maxi K+ channels and other K+ channels underlying resting Ga; 2) parallels between the Ba2+ and TEA+ sensitivities of Ga(V) and maxi K+ channels support a role for these channels in Ga(V); and 3) quinine has multiple effects on K(+)-conductive pathways in gallbladder epithelium, which are only partially explained by block of apical membrane maxi K+ channels.

Rat Prl and TSH secretion are regulated differently by K(+)-channel blockers

1994 ◽  
Vol 266 (1) ◽  
pp. E39-E43 ◽  
Author(s):  
X. Wang ◽  
T. Inukai ◽  
M. A. Greer ◽  
S. E. Greer
Keyword(s):  
Channel Blocker ◽  
Cell Types ◽  
Inhibitory Effect ◽  
Thyroid Stimulating Hormone ◽  
K Channel ◽  
Channel Blockers ◽  
Pituitary Cells ◽  
Dependent Manner ◽  
K Channels ◽  
Tsh Secretion

All four different K(+)-channel blockers [tetraethylammonium (TEA), a nonselective K(+)-channel blocker; tolbutamide, an ATP-sensitive K(+)-channel blocker; quinine and 4-aminopyridine, both primarily voltage-dependent K(+)-channel blockers] stimulated prolactin (Prl) secretion by acutely dispersed anterior pituitary cells but had no effect on thyroid-stimulating hormone (TSH) secretion. TEA stimulated Prl secretion in a dose-dependent manner between 1 microM and 20 mM, but even as high as 20 mM, TEA did not induce TSH secretion. Valinomycin (2 microM), a K+ ionophore, inhibited both basal and TEA-induced Prl secretion. TEA-stimulated Prl secretion was abolished by using a Ca(2+)-depleted medium or adding 10 microM dopamine. TEA did not reverse the inhibitory effect of dopamine on thyrotropin-releasing hormone-induced Prl secretion. Our data indicate that K+ channels may play a role in the secretion of adenohypophysial hormones that is idiosyncratic for each hormone. Differences in the role of K+ channels may reflect differences between the various pituitary cell types in plasma membrane ion channel composition, membrane potential, or the mechanism of exocytosis.

Isoflurane and Sevoflurane Induce Vasodilation of Cerebral Vessels via ATP-sensitive K+Channel Activation 

1998 ◽  
Vol 89 (4) ◽  
pp. 954-960 ◽  
Author(s):  
Hiroki Iida ◽  
Hiroto Ohata ◽  
Mami Iida ◽  
Yukinaga Watanabe ◽  
Shuji Dohi
Keyword(s):  
Adenosine Triphosphate ◽  
Volatile Anesthetic ◽  
Vessel Diameter ◽  
Cerebral Vessels ◽  
K Channel ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
K Channels ◽  
Cranial Window ◽  
Cerebral Vasodilation

Background Activation of adenosine triphosphate-sensitive K+ channels causes cerebral vasodilation. To assess their contribution to volatile anesthetic-induced cerebral vasodilation, the effects of glibenclamide, an adenosine triphosphate-sensitive K+ channel blocker, on the cerebral vasodilation induced by isoflurane and sevoflurane were studied. Methods Pentobarbital-anesthetized dogs (n = 24) assigned to one of two groups were prepared for measurement of pial vessel diameter using a cranial window preparation. Each dog received three minimum alveolar concentrations (MAC; 0.5, 1, and 1.5 MAC) of either isoflurane or sevoflurane, and the pial arteriolar diameters were measured in the presence or absence of glibenclamide (10(-5) M) infused continuously into the window. Mean arterial pressure was maintained with phenylephrine. Furthermore, to assess the direct effect of isoflurane and sevoflurane on cerebral vessels, artificial cerebrospinal fluid was administered topically by being bubbled with isoflurane or sevoflurane. The blocking effect of glibenclamide on the vasoactive effects of these anesthetics also were evaluated. Results Isoflurane and sevoflurane both significantly dilated large (> or = 100 microm) and small (< 100 microm) pial arterioles in a concentration-dependent manner (6% and 10%, 3% and 8% for 0.5 MAC; 10% and 19%, 7% and 14% for 1 MAC; 17% and 28%, 13% and 25% for 1.5 MAC). Glibenclamide attenuated the arteriolar dilation induced by these anesthetics (not significant in isoflurane). Topical application of isoflurane or sevoflurane dilated large and small arterioles both in a concentration-dependent manner. Such vasodilation was inhibited completely by glibenclamide. Conclusion The vasodilation of cerebral pial vessels induced by isoflurane and sevoflurane appears to be mediated, at least in part, via activation of adenosine triphosphate-sensitive K+ channels.

scholarly journals Redox Regulation of Large Conductance Ca2+-activated K+ Channels in Smooth Muscle Cells

1997 ◽  
Vol 110 (1) ◽  
pp. 35-44 ◽  
Author(s):  
Zhao-Wen Wang ◽  
Masayuki Nara ◽  
Yong-Xiao Wang ◽  
Michael I. Kotlikoff
Keyword(s):  
Redox Regulation ◽  
Channel Gating ◽  
K Channel ◽  
Dependent Manner ◽  
Channel Activity ◽  
Concentration Dependent Manner ◽  
K Channels ◽  
Sulfhydryl Oxidation ◽  
Excised Patches ◽  
Redox Agents

The effects of sulfhydryl reduction/oxidation on the gating of large-conductance, Ca2+-activated K+ (maxi-K) channels were examined in excised patches from tracheal myocytes. Channel activity was modified by sulfhydryl redox agents applied to the cytosolic surface, but not the extracellular surface, of membrane patches. Sulfhydryl reducing agents dithiothreitol, β-mercaptoethanol, and GSH augmented, whereas sulfhydryl oxidizing agents diamide, thimerosal, and 2,2′-dithiodipyridine inhibited, channel activity in a concentration-dependent manner. Channel stimulation by reduction and inhibition by oxidation persisted following washout of the compounds, but the effects of reduction were reversed by subsequent oxidation, and vice versa. The thiol-specific reagents N-ethylmaleimide and (2-aminoethyl)methanethiosulfonate inhibited channel activity and prevented the effect of subsequent sulfhydryl oxidation. Measurements of macroscopic currents in inside-out patches indicate that reduction only shifted the voltage/nPo relationship without an effect on the maximum conductance of the patch, suggesting that the increase in nPo following reduction did not result from recruitment of more functional channels but rather from changes of channel gating. We conclude that redox modulation of cysteine thiol groups, which probably involves thiol/disulfide exchange, alters maxi-K channel gating, and that this modulation likely affects channel activity under physiological conditions.

Halothane suppresses slow inward currents in hippocampal slices

1988 ◽  
Vol 66 (12) ◽  
pp. 1570-1575 ◽  
Author(s):  
K. Krnjević ◽  
E. Puil
Keyword(s):  
Hippocampal Slices ◽  
K Channel ◽  
Channel Blockers ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ca1 Neurons ◽  
Outward Currents ◽  
Electrode Voltage ◽  
Inward Currents ◽  
Ca Currents

Single-electrode voltage-clamp experiments were made on CA1 neurons in the presence of tetrodotoxin and K channel blockers. Applications of halothane (1–3% v/v) for 3–10 min caused a similar marked and reversible depression of slow inward currents (probably Ca currents) evoked by depolarizing pulses from a holding potential near−80 or near−40 mV. The peak amplitudes of the inward currents were much reduced, in a concentration-dependent manner, and they decayed more rapidly (half-decay time was shortened by a quarter). In most cases, leak conductances were diminished by halothane, making it unlikely that the suppression of inward currents was primarily caused by enhancement of outward currents. A similar inactivation of Ca currents in presynaptic terminals would explain why halothane depresses synaptic transmission.

Halothane and Isoflurane Decrease the Open State Probability of Potassium sup + Channels in Dog Cerebral Arterial Muscle Cells 

1995 ◽  
Vol 82 (2) ◽  
pp. 479-490 ◽  
Author(s):  
Hanna Eskinder ◽  
Debebe Gebremedhin ◽  
Joseph G. Lee ◽  
Nancy J. Rusch ◽  
Franjo D. Supan ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Muscle Cells ◽  
Volatile Anesthetics ◽  
State Probability ◽  
K Channel ◽  
Dependent Manner ◽  
External Application ◽  
Pipette Solution ◽  
K Channels ◽  
K Current

Background Both halothane and isoflurane evoke cerebral vasodilation. One of the potential mechanisms for arterial vasodilation is enhanced K+ efflux resulting from an increased opening frequency of membrane K+ channels. The current study was designed to determine the effects of volatile anesthetics on K+ channel current in single vascular smooth muscle cells isolated from dog cerebral arteries. Methods Patch clamp recording techniques were used to investigate the effects of volatile anesthetics on macroscopic and microscopic K+ channel currents. Results In the whole-cell patch-clamp mode, in cells dialyzed with pipette solution containing 2.5 mM EGTA and 1.8 mM CaCl2, depolarizing pulses from -60 to +60 mV elicited an outward K+ current that was blocked 65 +/- 5% by 3 mM tetraethylammonium (TEA). Halothane (0.4 and 0.9 mM) depressed the amplitude of this current by 18 +/- 4% and 34 +/- 6%, respectively. When 10 mM EGTA was used in the pipette solution to strongly buffer intracellular free Ca2+, an outward K+ current insensitive to 3 mM TEA was elicited. This K+ current, which was reduced 51 +/- 4% by 1 mM 4-aminopyridine, was also depressed by 17 +/- 5% and 29 +/- 7% with application of 0.4 and 0.9 mM halothane, respectively. In cell-attached patches using 145 mM KCl in the pipette solution and 5.2 mM KCl in the bath, the unitary conductance of the predominant channel type detected was 99 pS. External application of TEA (0.1 to 3 mM) reduced the unitary current amplitude of the 99 pS K+ channel in a concentration-dependent manner. The open state probability of this 99 pS K+ channel was increased by 1 microM Ca2+ ionophore (A23187). These findings indicate that the 99 pS channel measured in cell-attached patches was a TEA-sensitive, Ca(2+)-activated K+ channel. Halothane and isoflurane reversibly decreased the open state probability (NPo), mean open time, and frequency of opening of this 99 pS K+ channel without affecting single channel amplitude or the slope of the current-voltage relationship. Conclusions Halothane and isoflurane suppress the activity of K+ channels in canine cerebral arterial cells. These results suggest that mechanisms other than K+ channel opening likely mediate volatile anesthetic-induced vasodilation.

Functional coupling of Na(+)-K(+)-2Cl- cotransport and Ca(2+)-dependent K+ channels in vascular endothelial cells

1995 ◽  
Vol 269 (1) ◽  
pp. C267-C274 ◽  
Author(s):  
W. C. O'Neill ◽  
D. F. Steinberg
Keyword(s):  
Endothelial Cells ◽  
Cell Volume ◽  
Vascular Endothelial Cells ◽  
K Channel ◽  
Functional Coupling ◽  
Channel Blockers ◽  
Vascular Endothelial ◽  
Aortic Endothelial Cells ◽  
K Channels ◽  
Stimulation Of

To determine whether the activation of Na(+)-K(+)-2Cl- cotransport by Ca(2+)-mobilizing agonists is a direct effect of Ca2+ or is secondary to activation of Ca(2+)-dependent K+ channels [via cell shrinkage or decreased intracellular Cl- concentration ([Cl-]), we measured K+ fluxes in aortic endothelial cells in response to ATP and bradykinin. With either agonist there was an immediate bumetanide-insensitive efflux inhibitable by the K+ channel blockers tetrabutylammonium (TBA, 23 mM) and quinidine (1 mM), followed several minutes later by increased bumetanide-sensitive efflux or influx (Na(+)-K(+)-2Cl- cotransport). ATP induced a loss of cell K+ that was prevented by TBA and augmented by bumetanide. Both TBA and quinidine prevented the stimulation of cotransport by agonists but not by hypertonic shrinkage. Raising medium [K+] to prevent K+ loss also blocked activation of cotransport by agonists. The results indicate that the stimulation of Na(+)-K(+)-2Cl- cotransport by Ca2+ is not direct but instead is indirect via activation of Ca(2+)-dependent K+ channels and a resulting decrease in cell volume and intracellular [Cl-]. This suggests that at least one role of Na(+)-K(+)-2Cl- cotransport in endothelial cells is to maintain cell volume and intracellular [Cl-] during agonist stimulation.

scholarly journals The Role of K+, Ca2+ channels and Endothelial Hyperpolarizing Factors in Vasorelaxation Induced by Tribulus terrestris

2021 ◽  
Vol 2 (1) ◽  
pp. 94-100
Author(s):  
Thamer M. Bashir ◽  
Omar A.M. Al-Habib
Keyword(s):  
Methanolic Extract ◽  
K Channel ◽  
Tribulus Terrestris ◽  
Channel Blockers ◽  
Dependent Manner ◽  
The Novel ◽  
Concentration Dependent Manner ◽  
Relaxant Effect ◽  
Calcium Ion Channels

The present study focused on the relaxant effect of themethanolic extract (ME) of Tribulus terristris on rats’ thoracic aortae and included the study of underlying vasorelaxation mechanisms. The methanolic extract produced concentration-dependent relaxation in rats’ aorta. The methanolic extract produced concentration-dependent relaxation in the aortic rings. The use of different K+ channel blockers (BaCl2, 4-AP, GLIB, and TEA) indicated that Kv, KATP, KIR, and KCa and L-type Ca channels played no role in the methanolic extractinduced relaxation. However, with respect to endothelium-derived hyperpolarizing factors, PGI2 and sGC produced a mild inhibition in the relaxation response to ME while NO produced no effect at all. Based on the novel results of the current study, it can be concluded that T. terrestris methanolic extract (ME) mediated relaxation in isolated rat aortic tissues in a concentration-dependent manner. Moreover, we discovered that ME-mediated relaxation is endothelium-dependent and that potassium and calcium ion channels play no role in this relaxation with a limited role of PGI2 and sGC.

scholarly journals Voltage-gated potassium channels are required for human T lymphocyte activation.

1984 ◽  
Vol 160 (2) ◽  
pp. 369-385 ◽  
Author(s):  
K G Chandy ◽  
T E DeCoursey ◽  
M D Cahalan ◽  
C McLaughlin ◽  
S Gupta
Keyword(s):  
Protein Synthesis ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Lymphocyte Activation ◽  
K Channel ◽  
Channel Blockers ◽  
Dependent Manner ◽  
Two Dimensional Gel Electrophoresis ◽  
K Channels ◽  
T Lymphocyte Activation

The calcium channel blockers, verapamil and diltiazem, inhibit phytohemagglutinin (PHA)-induced mitogenesis at concentrations that block the T lymphocyte K channel currents. K channel blockers also inhibit the allogeneic mixed lymphocyte response in a dose-dependent manner with the same potency sequence as for block of K currents. K channel blockers inhibit PHA-stimulated mitogenesis only if added during the first 20-30 h after PHA addition, but not later, indicating a requirement for functional K channels during this period. We investigated the effect of K channel blockers on various aspects of protein synthesis for two reasons: first, protein synthesis appears to be necessary for the events leading to DNA synthesis, and second, the increase in the protein synthetic rate commences during the first 24-48 h after PHA addition. PHA-induced total protein synthesis was reduced to the level in unstimulated T lymphocytes by K channel blockers in a dose-dependent manner with the same potency sequence as for the block of K currents and inhibition of [3H]thymidine incorporation. Two-dimensional gel electrophoresis demonstrated that although the synthesis of the majority of proteins was reduced by K channel blockers to the level in unstimulated T cells, some proteins continued to be synthesized at an enhanced rate compared with resting cells. Two proteins, S and T, detected by two-dimensional gel electrophoresis in unstimulated T lymphocytes, appeared to be reduced in intensity in gels of PHA-treated T lymphocytes, in contrast to the increased synthesis of the remaining proteins. 4-Aminopyridine (4-AP), at concentrations that inhibit protein synthesis, prevented the apparent PHA-induced reduction of proteins S and T. These proteins may play a role in maintaining the T lymphocyte in a resting state and may be related to the translation inhibitory factors reported to be present at a higher specific activity in quiescent T lymphocytes than in PHA-activated T cells. The expression of the IL-2 receptor (Tac) during T lymphocyte activation was not altered by K channel blockers, whereas the production of interleukin 2 (IL-2) was reduced to the level in unstimulated T lymphocytes. Exogenous IL-2 partially relieved the inhibition of mitogenesis by low, but not by high, concentrations of 4-AP. These experiments clarify the role of K channels in T lymphocyte activation and suggest that functional K channels are required either for protein synthesis or for events leading to protein synthesis.

Sign in / Sign up

Export Citation Format

Share Document