Bethanidine increases one type of potassium current and relaxes aortic muscle

1988 ◽  
Vol 66 (6) ◽  
pp. 731-736 ◽  
Author(s):  
G. Bkaily ◽  
J.-P. Caillé ◽  
M. D. Payet ◽  
M. Peyrow ◽  
R. Sauvé ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Vascular Smooth Muscle ◽  
Potassium Current ◽  
Single Cells ◽  
Rabbit Aorta ◽  
Cell Voltage ◽  
Resting Membrane Potential ◽  
Delayed Rectifier ◽  
Voltage Dependent

Using a whole-cell voltage-clamp technique, we identified two time- and voltage-dependent K+ currents: an early outward rectifier and a delayed outward rectifier in single vascular smooth muscle cells of rabbit aorta in culture. About 90% of the single cells tested showed a predominant delayed outward K+ current type. Both K+ currents were decreased by tetraethylammonium. In contrast, bethanidine sulphate (10−4 M), a pharmacological analog of the cardiac antifibrillatory drug, bretylium tosylate, decreased the early outward K+ current, increased the delayed rectifier K+ current type, and hyperpolarized the resting membrane potential. Bethanidine was found to relax vascular smooth muscle. The vasodilatory effect of bethanidine is associated with the activation of a K+ current that is probably involved in keeping the membrane potential at the resting state, thereby depressing the excitability of the aortic vascular smooth muscle.

Role of HERG-like K+ currents in opossum esophageal circular smooth muscle

1999 ◽  
Vol 277 (6) ◽  
pp. C1284-C1290 ◽  
Author(s):  
Hamid I. Akbarali ◽  
Hemant Thatte ◽  
Xue Dao He ◽  
Wayne R. Giles ◽  
Raj K. Goyal
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Smooth Muscle Cells ◽  
Single Cells ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Resting Membrane Potential ◽  
Channel Blockers ◽  
Circular Smooth Muscle ◽  
Inward Currents

An inwardly rectifying K+ conductance closely resembling the human ether-a-go-go-related gene (HERG) current was identified in single smooth muscle cells of opossum esophageal circular muscle. When cells were voltage clamped at 0 mV, in isotonic K+ solution (140 mM), step hyperpolarizations to −120 mV in 10-mV increments resulted in large inward currents that activated rapidly and then declined slowly (inactivated) during the test pulse in a time- and voltage- dependent fashion. The HERG K+ channel blockers E-4031 (1 μM), cisapride (1 μM), and La3+ (100 μM) strongly inhibited these currents as did millimolar concentrations of Ba2+. Immunoflourescence staining with anti-HERG antibody in single cells resulted in punctate staining at the sarcolemma. At membrane potentials near the resting membrane potential (−50 to −70 mV), this K+ conductance did not inactivate completely. In conventional microelectrode recordings, both E-4031 and cisapride depolarized tissue strips by 10 mV and also induced phasic contractions. In combination, these results provide direct experimental evidence for expression of HERG-like K+ currents in gastrointestinal smooth muscle cells and suggest that HERG plays an important role in modulating the resting membrane potential.

Physiological role of Ca(2+)-activated and voltage-dependent K+ currents in rabbit coronary myocytes

1994 ◽  
Vol 266 (6) ◽  
pp. C1523-C1537 ◽  
Author(s):  
N. Leblanc ◽  
X. Wan ◽  
P. M. Leung
Keyword(s):  
Steady State ◽  
Membrane Potential ◽  
Physiological Role ◽  
Cell Voltage ◽  
Resting Membrane Potential ◽  
Physiological Level ◽  
Steady State Current ◽  
Voltage Dependent ◽  
A Minor ◽  
And Function

The properties and function of Ca(2+)-activated K+ (KCa) and voltage-dependent K+ (IK) currents of rabbit coronary myocytes were studied under whole cell voltage-clamp conditions (22 degrees C). Inhibition of KCa by tetraethylammonium chloride (1-10 mM) or charybdotoxin (50-100 nM) suppressed noisy outward rectifying current elicited by 5-s voltage steps or ramp at potentials > 0 mV, reduced the hump of the biphasic ramp current-voltage relation, and shifted by less than +5 mV the potential at which no net steady-state current is recorded (Enet; index of resting membrane potential). Inhibition of steady-state inward Ca2+ currents [ICa(L)] by nifedipine (1 microM) displaced Enet by -11 mV. Analysis of steady-state voltage dependence of IK supported the existence of a "window" current between -50 and 0 mV. 4-Aminopyridine (2 mM) blocked a noninactivating component of IK evoked between -30 and -40 mV, abolished the hump current during ramps, and shifted Enet by more than +15 mV; hump current persisted during 2-min ramp depolarizations and peaked near the maximum overlap of the steady-state activation and inactivation curves of IK (about -22 mV). A threefold rise in extracellular Ca2+ concentration (1.8-5.4 mM) enhanced time-dependent outward K+ current (6.7-fold at +40 mV) and shifted Enet by -30 mV. It is concluded that, under steady-state conditions, IK and ICa(L) play a major role in regulating resting membrane potential at a physiological level of intracellular Ca2+ concentration, with a minor contribution from KCa. However, elevation of intracellular Ca2+ concentration enhances KCa and hyperpolarizes the myocyte to limit Ca2+ entry through ICa(L).

48-h Hypoxic exposure results in endothelium-dependent systemic vascular smooth muscle cell hyperpolarization

2002 ◽  
Vol 283 (1) ◽  
pp. R79-R85 ◽  
Author(s):  
Scott Earley ◽  
Jay S. Naik ◽  
Benjimen R. Walker
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Vascular Smooth Muscle ◽  
Vessel Wall ◽  
Hypoxic Exposure ◽  
Resting Membrane Potential ◽  
Resistance Arteries ◽  
Adrenergic Agonist ◽  
Intracellular Ca ◽  
Oxide Synthase

Chronic hypoxia (CH) results in reduced sensitivity to vasoconstrictors in conscious rats that persists upon restoration of normoxia. We hypothesized that this effect is due to endothelium-dependent hyperpolarization of vascular smooth muscle (VSM) cells after CH. VSM cell resting membrane potential was determined for superior mesenteric artery strips isolated from CH rats (Pb = 380 Torr for 48 h) and normoxic controls. VSM cells from CH rats studied under normoxia were hyperpolarized compared with controls. Resting vessel wall intracellular Ca2+ concentration ([Ca2+]i) and pressure-induced vasoconstriction were reduced in vessels isolated from CH rats compared with controls. Vasoconstriction and increases in vessel wall [Ca2+]i in response to the α1-adrenergic agonist phenylephrine (PE) were also blunted in resistance arteries from CH rats. Removal of the endothelium normalized resting membrane potential, resting vessel wall [Ca2+]i, pressure-induced vasoconstrictor responses, and PE-induced constrictor and Ca2+ responses between groups. Whereas VSM cell hyperpolarization persisted in the presence of nitric oxide synthase inhibition, heme oxygenase inhibition restored VSM cell resting membrane potential in vessels from CH rats to control levels. We conclude that endothelial derived CO accounts for persistent VSM cell hyperpolarization and vasoconstrictor hyporeactivity after CH.

Regulation of 4-aminopyridine-sensitive, delayed rectifier K+ channels in vascular smooth muscle by phosphorylation

1996 ◽  
Vol 74 (4) ◽  
pp. 439-447 ◽  
Author(s):  
W. C. Cole ◽  
O. Clément-Chomienne ◽  
E. A. Aiello
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Membrane Potential ◽  
Protein Kinase ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Protein ◽  
Muscle Cells ◽  
Delayed Rectifier ◽  
Kinase C

Voltage-gated, delayed rectifier K+ current (KV) that is sensitive to 4-aminopyridine (4AP) block has been identified in all vascular smooth muscle tissues studied to date. These channels conduct outward, hyperpolarizing K+ current that influences resting membrane potential and contributes to repolarization of action potentials. Smooth muscle cells in most arterial resistance vessels regulate Ca2+ influx and contractile tone by low amplitude, tonic changes in membrane potential. Block of KV with 4-aminopyridine leads to contraction and an enhanced myogenic response to increased intravascular pressure. We investigated the modulation of KV currents in isolated, freshly dispersed smooth muscle cells from rabbit portal vein and coronary arteries in whole-cell voltage clamp experiments. Our findings indicate that KV channels are regulated by signal transduction mechanisms involving vasoactive agonists that activate cAMP-dependent protein kinase (PKA) or protein kinase C (PKC). In this paper, the properties and potential function of KV channels in vascular smooth muscle are reviewed. Further, the regulation and potential role of alterations in KV due to β-adrenoceptor agonists, adenylyl cyclase and PKA, as well as angiotensin II, diacylglycerol, and PKC are discussed.Key words: potassium channels, smooth muscle, protein kinase A, protein kinase C, membrane potential.

Parathyroid hypertensive factor inhibits voltage-gated K+ channels in vascular smooth muscle cells

1999 ◽  
Vol 77 (11) ◽  
pp. 860-865 ◽  
Author(s):  
Jun Ren ◽  
Lei Zhang ◽  
Christina G Benishin
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Time Dependent ◽  
Delayed Rectifier ◽  
K Channels ◽  
Parathyroid Hypertensive Factor

Parathyroid hypertensive factor (PHF) has been implicated in regulation of vascular smooth muscle tone and pathogenesis of several forms of hypertension. Earlier studies have suggested that PHF enhances the actions of other vasoconstrictors, while it has no in vitro vasoconstrictor property of its own. PHF was previously found to enhance the L-type Ca channel currents and intracellular Ca responses to depolarization in vascular smooth muscle cells (VSMCs). The present study examined whether PHF might act on K channels in the plasma membrane of VSMCs. Primary cultured VSMCs from rat tail artery were used. The whole-cell version of the patch-clamp technique was used under conditions in which there was no contribution of Ca-activated K channels to the outward current. Both purified and semipurified PHF inhibited the delayed rectifier type potassium current in a dose-dependent manner. The effect was time dependent and was first significantly different from the control current after 30 min. The inhibition of the delayed rectifier K channel was associated with a time-dependent decrease in the resting membrane potential. Therefore, PHF may alter VSMC cellular Ca responses by reducing the membrane potential to a level closer to the activation potential of Ca channels.Key words: parathyroid hypertensive factor, hypertension, potassium channels, vascular smooth muscle, membrane potential.

Effect of chronic hypoxia on K+ channels: regulation in human pulmonary vascular smooth muscle cells

1997 ◽  
Vol 272 (4) ◽  
pp. C1271-C1278 ◽  
Author(s):  
W. Peng ◽  
J. R. Hoidal ◽  
S. V. Karwande ◽  
I. S. Farrukh
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Chronic Hypoxia ◽  
Muscle Cells ◽  
K Channel ◽  
Resting Membrane Potential ◽  
Delayed Rectifier ◽  
Voltage Dependent ◽  
Dependent Protein ◽  
Pulmonary Arterial

We investigated the effects of chronic hypoxia on the major outward K+ currents in early cultured human main pulmonary arterial smooth muscle cells (HPSMC). Unitary currents were measured from inside-out, outside-out, and cell-attached patches of HPSMC. Chronic hypoxia depolarized resting membrane potential (Em) and reduced the activity of a charybdotoxin (CTX)- and iberiotoxin-sensitive, Ca2+-dependent K+ channel (KCa). The 4-aminopyridine-sensitive and CTX-insensitive channel or the delayed rectifier K+ channel was unaffected by chronic hypoxia. Chronic hypoxia caused a +33- to +53-mV right shift in voltage-dependent activation of K(Ca) and a decrease in K(Ca) activity at all cytosolic Ca2+ concentrations ([Ca2+]i) in the range of 0.1-10 microM. Thus the hypoxia-induced decrease in K(Ca) activity was most likely due to a decrease in K(Ca) sensitivity to Em and [Ca2+]i. Chronic hypoxia reduced the ability of nitric oxide (NO.) and guanosine 3',5'-cyclic monophosphate (cGMP) to activate K(Ca). The cGMP-dependent protein kinase-induced activation of K(Ca) was also significantly inhibited by chronic hypoxia. In addition, inhibiting channel dephosphorylation with calyculin A caused significantly less increase in K(Ca) activity in membrane patches excised from chronically hypoxic HPSMC compared with normoxic controls. This suggests that the mechanism by which hypoxia modulates NO.-induced K(Ca) activation is by decreasing the NO./cGMP-mediated phosphorylation of the channel.

Resting calcium influx in airway smooth muscle

2005 ◽  
Vol 83 (8-9) ◽  
pp. 717-723 ◽  
Author(s):  
Luis M Montaño ◽  
Blanca Bazán-Perkins
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Calcium Influx ◽  
Physiological Role ◽  
Resting Membrane Potential ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
Influx Pathways

Plasma membrane Ca2+ leak remains the most uncertain of the cellular Ca2+ regulation pathways. During passive Ca2+ influx in non-stimulated smooth muscle cells, basal activity of constitutive Ca2+ channels seems to be involved. In vascular smooth muscle, the 3 following Ca2+ entry pathways contribute to this phenomenon: (i) via voltage-dependent Ca2+ channels, (ii) receptor gated Ca2+ channels, and (iii) store operated Ca2+ channels, although, in airway smooth muscle it seems only 2 passive Ca2+ influx pathways are implicated, one sensitive to SKF 96365 (receptor gated Ca2+ channels) and the other to Ni2+ (store operated Ca2+ channels). Resting Ca2+ entry could provide a sufficient amount of Ca2+ and contribute to resting intracellular Ca2+ concentration ([Ca2+]i), maintenance of the resting membrane potential, myogenic tone, and sarcoplasmic reticulum-Ca2+ refilling. However, further research, especially in airway smooth muscle, is required to better explore the physiological role of this passive Ca2+ influx pathway as it could be involved in airway hyperresponsiveness.Key words: basal Ca2+ entry, constitutive Ca2+ channels, airway and vascular smooth muscle, SKF 96365, Ni2+.

Membrane potential of vascular smooth muscle and hypertension in spontaneously hypertensive rats

1984 ◽  
Vol 62 (8) ◽  
pp. 957-960 ◽  
Author(s):  
D. W. Cheung
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Membrane Potential ◽  
Vascular Smooth Muscle ◽  
Spontaneously Hypertensive Rats ◽  
Chronic Treatment ◽  
Resting Membrane Potential ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

The resting membrane potential of tail arteries from spontaneously hypertensive rats (SHRs) and Wistar-Kyoto controls (WKYs) was compared. At 4–5 weeks old, the blood pressure and resting membrane potential of the SHRs was not significantly different from the WKYs. The blood pressure of 8- to 10-week-old SHRs increased significantly to 183 mmHg (1 mmHg = 133.322 Pa) from 127 mmHg at 4 weeks, and the membrane potential decreased from 60 to 51 mV. At 15 weeks of age, the blood pressure of the SHRs was 193 mmHg and the membrane potential was 49 mV. In WKYs, there was no significant change in membrane potential with age. The decrease in membrane potential in the SHRs is due to a decrease in the ouabain-sensitive electrogenic pumping. Chronic treatment of the SHRs with captopril (100 mg∙kg−1∙day−1) prevented the increase in blood pressure and the decrease in membrane potential.

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