scholarly journals Exercise training increases K+-channel contribution to regulation of coronary arterial tone

1998 ◽  
Vol 84 (4) ◽  
pp. 1225-1233 ◽  
Author(s):  
D. K. Bowles ◽  
M. H. Laughlin ◽  
M. Sturek
Keyword(s):  
Membrane Potential ◽  
Exercise Training ◽  
Sodium Nitroprusside ◽  
K Channel ◽  
Resting Membrane Potential ◽  
Channel Blockers ◽  
Miniature Swine ◽  
Isolated Cells ◽  
Resting Tension ◽  
Basal Tone

The present study examined whether regulation of coronary tone in conduit arteries (>1.0 mm ID) is altered by exercise training. Yucatan miniature swine were treadmill trained for 16–20 wk (Ex) and compared with sedentary counterparts (Sed). Endothelium-denuded arterial rings were stretched to optimal length and allowed to equilibrate for 60 min. Inhibition of either Ca2+-activated channels [1 mM tetraethylammonium (TEA) or 10 nM iberiotoxin (IBTX)] or voltage-dependent K+ channels [1 mM 4-aminopyridine (4-AP)] significantly increased resting tension in both groups; however, the effect of all K+-channel blockers was greater in Ex. Addition of 1 mM sodium nitroprusside reduced resting tension in both groups, confirming the presence of active basal tone; however, sodium nitroprusside-sensitive tone was increased approximately twofold in Ex compared with Sed group. Perforated patch-clamp experiments on isolated smooth muscle cells demonstrated no effect of exercise training on whole cell TEA-sensitive, 4-AP-sensitive, or basal K+ current. Similarly, whereas TEA, 4-AP, and IBTX all decreased resting membrane potential, there was no difference in depolarization between groups. The greater effect of TEA on resting tension in Ex could be mimicked in Sed by addition of the Ca2+-channel agonist BAY K 8644. In conclusion, the greater response to K+-channel blockers after exercise training is consistent with an increased contribution of K+ channels to regulation of basal tone in conduit coronary arteries. The lack of an effect of training on K+ current characteristics or membrane potential responses in isolated cells suggests that a requisite factor for enhanced K+-channel activation in arteries from Ex, possibly stretch, is absent in isolated cells.

Gender-specific K+-channel contribution to adenosine-induced relaxation in coronary arterioles

2002 ◽  
Vol 92 (2) ◽  
pp. 550-558 ◽  
Author(s):  
Cristine L. Heaps ◽  
Douglas K. Bowles
Keyword(s):  
Nitric Oxide ◽  
Intraluminal Pressure ◽  
K Channel ◽  
Apical Region ◽  
Channel Blockers ◽  
Miniature Swine ◽  
Basal Diameter ◽  
Male And Female ◽  
Basal Tone ◽  
Coronary Arterioles

We examined the contribution of K+-channel activity on basal tone and adenosine-mediated relaxation of coronary arterioles isolated from sexually mature male and female miniature swine. Arterioles (∼100–200 μm ID) isolated from the apical region of the heart were cannulated and studied using videodimensional analysis under constant intraluminal pressure. Coronary arterioles from male and female pigs demonstrated similar levels of basal tone and reductions in basal diameter in response to the K+-channel blockers 4-aminopyridine (4-AP; 1 mM), tetraethylammonium (1 mM), and glibenclamide (Glib; 10 μM), with 4-AP producing significantly greater constriction than tetraethylammonium or Glib. After endothelin-induced preconstriction, relaxation responses to adenosine were not significantly different between coronary arterioles of male and female pigs. Inhibition of 4-AP-sensitive channels significantly impaired adenosine-mediated relaxation in arterioles from male but not female pigs. However, inhibition of K+ channels with iberiotoxin (100 nM) or Glib had no effect on adenosine-induced relaxation in either sex. Results obtained in the presence of nitric oxide synthase inhibition suggest a potential interaction of 4-AP-sensitive channels and nitric oxide at low adenosine concentrations. In conclusion, our data indicate that 4-AP-sensitive channels 1) contribute significantly to basal tone in coronary arterioles of both male and female pigs, 2) contribute to adenosine-mediated relaxation in male but not female pigs, and 3) can contribute to adenosine-induced relaxation independent of nitric oxide production in male pigs. These data are consistent with a significant role for voltage-dependent K+channels in adenosine-mediated relaxation of coronary arterioles from males.

scholarly journals Activation of Ca(2+)-dependent K+ current by acetylcholine and histamine in a human gastric epithelial cell line.

1993 ◽  
Vol 102 (4) ◽  
pp. 667-692 ◽  
Author(s):  
E Hamada ◽  
T Nakajima ◽  
S Ota ◽  
A Terano ◽  
M Omata ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Epithelial Cell ◽  
Cell Line ◽  
K Channel ◽  
Resting Membrane Potential ◽  
Induced Response ◽  
Epithelial Cell Line ◽  
Bathing Solution ◽  
Pipette Solution ◽  
K Current

The effects of acetylcholine (ACh) and histamine (His) on the membrane potential and current were examined in JR-1 cells, a mucin-producing epithelial cell line derived from human gastric signet ring cell carcinoma. The tight-seal, whole cell clamp technique was used. The resting membrane potential, the input resistance, and the capacitance of the cells were approximately -12 mV, 1.4 G ohms, and 50 pF, respectively. Under the voltage-clamp condition, no voltage-dependent currents were evoked. ACh or His added to the bathing solution hyperpolarized the membrane by activating a time- and voltage-independent K+ current. The ACh-induced hyperpolarization and K+ current persisted, while the His response desensitized quickly (< 1 min). These effects of ACh and His were mediated predominantly by m3-muscarinic and H1-His receptors, respectively. The K+ current induced by ACh and His was inhibited by charybdotoxin, suggesting that it is a Ca(2+)-activated K+ channel current (IK.Ca). The measurement of intracellular Ca2+ ([Ca2+]i) using Indo-1 revealed that both agents increased [Ca2+]i with similar time courses as they increased IK.Ca. When EGTA in the pipette solution was increased from 0.15 to 10 mM, the induction of IK.Ca by ACh and His was abolished. Thus, both ACh and His activate IK.Ca by increasing [Ca2+]i in JR-1 cells. In the Ca(2+)-free bathing solution (0.15 mM EGTA in the pipette), ACh evoked IK.Ca transiently. Addition of Ca2+ (1.8 mM) to the bath immediately restored the sustained IK.Ca. These results suggest that the ACh response is due to at least two different mechanisms; i.e., the Ca2+ release-related initial transient activation and the Ca2+ influx-related sustained activation of IK.Ca. Probably because of desensitization, the Ca2+ influx-related component of the His response could not be identified. Intracellularly applied inositol 1,4,5-trisphosphate (IP3), with and without inositol 1,3,4,5-tetrakisphosphate (IP4), mimicked the ACh response. IP4 alone did not affect the membrane current. Under the steady effect of IP3 or IP3 plus IP4, neither ACh nor His further evoked IK.Ca. Intracellular application of heparin or of the monoclonal antibody against the IP3 receptor, mAb18A10, inhibited the ACh and His responses in a concentration-dependent fashion. Neomycin, a phospholipase C (PLC) inhibitor, also inhibited the agonist-induced response in a concentration-dependent fashion. Although neither pertussis toxin (PTX) nor N-ethylmaleimide affected the ACh or His activation of IK,Ca, GDP beta S attenuated and GTP gamma S enhanced the agonist response.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

Acute reductions in PO2 depolarize pulmonary artery endothelial cells and decrease [Ca2+]i

1994 ◽  
Vol 266 (4) ◽  
pp. H1416-H1421 ◽  
Author(s):  
T. Stevens ◽  
D. N. Cornfield ◽  
I. F. McMurtry ◽  
D. M. Rodman
Keyword(s):  
Endothelial Cells ◽  
Membrane Potential ◽  
Pulmonary Artery ◽  
Driving Force ◽  
Primary Cultures ◽  
K Channel ◽  
Channel Blockers ◽  
Electrochemical Gradient ◽  
Similar Reduction ◽  
Fura 2

Whereas pulmonary artery endothelial cells (PAECs) are sensitive to oxygen, neither the effect of an acute reduction in PO2 on PAEC membrane potential nor its effect on intracellular free Ca2+ ([Ca2+]i) is known. We hypothesized that in confluent primary cultures of PAECs, an acute decrease in PO2 would depolarize the cell membrane, inhibit Ca2+ influx, and reduce [Ca2+]i. To test this hypothesis, the membrane-sensitive fluorophore bis (1,3-dibutylbarbituric acid) trimethine oxonol (DiBAC4, 1 microM) and [Ca2+]i-sensitive probe fura 2 (3 microM) were used. A decrease in PO2 from 125 to 35 mmHg caused membrane depolarization and a 60 +/- 8% (data are means +/- SE) reduction in Ca2+ influx, estimated by manganese quenching of fura 2 fluorescence. While basal [Ca2+]i was 79 +/- 5 nM in normoxic cells, it decreased to 31 +/- 2 nM after 15 min of hypoxia. Decreasing the electrochemical gradient for Ca2+ entry with either low extracellular Ca2+, the K+ channel blockers tetraethylammonium or charybdotoxin, or blockade of Ca2+ entry with lanthanum decreased [Ca2+]i by 54-71% of that observed during an acute reduction in PO2. These results demonstrate that an acute reduction in PO2 1) depolarizes PAECs, 2) reduces Ca2+ influx, and 3) decreases [Ca2+]i, and that a similar reduction in [Ca2+]i was observed with interventions designed to reduce the electrochemical driving force for Ca2+ entry.

Opposing roles of K+and Cl−channels in maintenance of opossum lower esophageal sphincter tone

2000 ◽  
Vol 279 (6) ◽  
pp. G1226-G1234 ◽  
Author(s):  
Yong Zhang ◽  
David V. Miller ◽  
William G. Paterson
Keyword(s):  
Lower Esophageal Sphincter ◽  
Circular Muscle ◽  
Isometric Tension ◽  
Niflumic Acid ◽  
Resting Membrane Potential ◽  
Channel Blockers ◽  
Microelectrode Recordings ◽  
Basal Tone ◽  
Esophageal Sphincter

The ionic basis underlying the maintenance of myogenic tone of lower esophageal sphincter circular muscle (LES) was investigated in opossum with the use of standard isometric tension and conventional intracellular microelectrode recordings in vitro. In tension recording studies, nifedipine (1 μM) reduced basal tone to 27.7 ± 3.8% of control. The K+channel blockers tetraethylammonium (TEA, 2 mM), charybdotoxin (100 nM), and 4-aminopyridine (4-AP, 2 mM) enhanced resting tone, whereas apamin and glibenclamide were without affect. Cl−channel blockers DIDS (500 μM) and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (500 μM), as well as niflumic acid (0.1–300 μM), decreased basal tone, but tamoxifen was without effect. Intracellular microelectrode recordings revealed ongoing, spontaneous, spike-like action potentials (APs). Nifedipine abolished APs and depolarized resting membrane potential (RMP). Both TEA and 4-AP significantly depolarized RMP and augmented APs, whereas niflumic acid dose-dependently hyperpolarized RMP and abolished APs. These data suggest that, in the opossum, basal tone is associated with continuous APs and that K+and Ca2+-activated Cl−channels have important opposing roles in the genesis of LES tone.

scholarly journals The resting membrane potential of hSC-CM in a syncytium is more hyperpolarised than that of isolated cells

Channels ◽  
2021 ◽  
Vol 15 (1) ◽  
pp. 239-252
Author(s):  
Dieter V. Van de Sande ◽  
Ivan Kopljar ◽  
Alaerts Maaike ◽  
Ard Teisman ◽  
David J. Gallacher ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Resting Membrane Potential ◽  
Isolated Cells

Exercise training restores adenosine-induced relaxation in coronary arteries distal to chronic occlusion

2000 ◽  
Vol 278 (6) ◽  
pp. H1984-H1992 ◽  
Author(s):  
Cristine L. Heaps ◽  
Michael Sturek ◽  
Julie A. Rapps ◽  
M. Harold Laughlin ◽  
Janet L. Parker
Keyword(s):  
Coronary Artery ◽  
Exercise Training ◽  
Sodium Nitroprusside ◽  
Coronary Arteries ◽  
Coronary Occlusion ◽  
Circumflex Coronary Artery ◽  
Miniature Swine ◽  
Chronic Occlusion ◽  
Chronic Coronary Occlusion ◽  
Camp And Cgmp

We previously reported that canine collateral-dependent coronary arteries exhibit impaired relaxation to adenosine but not sodium nitroprusside. In contrast, exercise training enhances adenosine sensitivity of normal porcine coronary arteries. These results stimulated the hypothesis that chronic coronary occlusion and exercise training produce differential effects on cAMP- versus cGMP-mediated relaxation. To test this hypothesis, Ameroid occluders were surgically placed around the proximal left circumflex coronary artery (LCx) of female Yucatan miniature swine 8 wk before initiating sedentary or exercise training (treadmill run, 16 wk) protocols. Relaxation to the cAMP-dependent vasodilators adenosine (10− 7 to 10− 3 M) and isoproterenol (3 × 10− 8 to 3 × 10− 5 M) were impaired in collateral-dependent LCx versus nonoccluded left anterior descending (LAD) arterial rings isolated from sedentary but not exercise-trained pigs. Furthermore, adenosine-mediated reductions in simultaneous tension and myoplasmic free Ca2+ were impaired in LCx versus LAD arteries isolated from sedentary but not exercise-trained pigs. In contrast, relaxation in response to the cAMP-dependent vasodilator forskolin (10− 9 to 10− 5 M) and the cGMP-dependent vasodilator sodium nitroprusside (10− 9 to 10− 4 M) was not different in LCx versus LAD arteries of sedentary or exercise-trained animals. These data suggest that chronic occlusion impairs receptor-dependent, cAMP-mediated relaxation; receptor-independent cAMP- and cGMP-mediated relaxation were unimpaired. Importantly, exercise training restores cAMP-mediated relaxation of collateral-dependent coronary arteries.

The effect of diazepam on potassium contractures, contraction threshold, and resting tension in rat skeletal muscles

1988 ◽  
Vol 66 (5) ◽  
pp. 573-579 ◽  
Author(s):  
Michael Chua ◽  
Angela F. Dulhunty
Keyword(s):  
Membrane Potential ◽  
Type Equation ◽  
Resting Membrane Potential ◽  
Muscle Fibres ◽  
High Potassium ◽  
Fourfold Increase ◽  
Maximum Tension ◽  
Potassium Contracture ◽  
Negative Shift ◽  
Resting Tension

The effects of diazepam on potassium contractures, contraction threshold, and resting tension have been examined in rat soleus muscle fibres. Two actions of the drug were defined that could not be attributed to changes in the resting membrane potential or depolarization in high potassium solutions. The major effect was an increase in the amplitude of submaximal tension during either twitches or potassium contractures and an increase in resting tension. At 400 μM diazepam, there was (a) a fourfold increase in 40 mM potassium contracture tension, (b) a negative shift of 8 mV in the membrane potential for half maximum tension estimated from the best fit of a Boltzmann-type equation to average potassium contracture data, (c) a negative shift of 8 mV in the threshold for contraction measured under voltage clamp conditions, and (d) a contracture of variable amplitude to a level that was occasionally equivalent to maximum tetanic tension. These potentiating actions of diazepam depended on drag concentration within the range of 100–800 μM. In contrast, the second effect of diazepam, depression of maximum tension by 10–15%, was independent of drug concentration between 100 and 400 μM. The results support the idea that diazepam produces an increase in resting myoplasmic calcium concentrations.

scholarly journals Contribution of KCNQ and TREK Channels to the Resting Membrane Potential in Sympathetic Neurons at Physiological Temperature

2020 ◽  
Vol 21 (16) ◽  
pp. 5796
Author(s):  
Paula Rivas-Ramírez ◽  
Antonio Reboreda ◽  
Lola Rueda-Ruzafa ◽  
Salvador Herrera-Pérez ◽  
Jose Antonio Lamas
Keyword(s):  
Membrane Potential ◽  
Room Temperature ◽  
Sympathetic Neurons ◽  
K Channel ◽  
Resting Membrane Potential ◽  
Physiological Temperature ◽  
M Current ◽  
Key Players ◽  
Cervical Ganglion ◽  
Ionic Mechanisms

The ionic mechanisms controlling the resting membrane potential (RMP) in superior cervical ganglion (SCG) neurons have been widely studied and the M-current (IM, KCNQ) is one of the key players. Recently, with the discovery of the presence of functional TREK-2 (TWIK-related K+ channel 2) channels in SCG neurons, another potential main contributor for setting the value of the resting membrane potential has appeared. In the present work, we quantified the contribution of TREK-2 channels to the resting membrane potential at physiological temperature and studied its role in excitability using patch-clamp techniques. In the process we have discovered that TREK-2 channels are sensitive to the classic M-current blockers linopirdine and XE991 (IC50 = 0.310 ± 0.06 µM and 0.044 ± 0.013 µM, respectively). An increase from room temperature (23 °C) to physiological temperature (37 °C) enhanced both IM and TREK-2 currents. Likewise, inhibition of IM by tetraethylammonium (TEA) and TREK-2 current by XE991 depolarized the RMP at room and physiological temperatures. Temperature rise also enhanced adaptation in SCG neurons which was reduced due to TREK-2 and IM inhibition by XE991 application. In summary, TREK-2 and M currents contribute to the resting membrane potential and excitability at room and physiological temperature in the primary culture of mouse SCG neurons.

Effect of aminophylline-Ca2+ blocker interaction on membrane potential of rat diaphragm fibers

1993 ◽  
Vol 74 (6) ◽  
pp. 2745-2749 ◽  
Author(s):  
O. Delbono ◽  
B. A. Kotsias
Keyword(s):  
Membrane Potential ◽  
Calcium Channel ◽  
Calcium Channel Blockers ◽  
Intrinsic Activity ◽  
Resting Membrane Potential ◽  
Maximum Effect ◽  
Channel Blockers ◽  
Dependent Manner ◽  
Rat Diaphragm

We studied the antagonism between aminophylline and two calcium channel blockers, nifedipine and verapamil, and its effect on the resting membrane potential of rat diaphragm fibers in vitro at 25 degrees C. Aminophylline hyperpolarizes the fibers in a dose-dependent manner, and the maximum effect is reached with 1 mM of the drug, approximately 9 mV compared with normal values. Both nifedipine and verapamil (1–5 microM) decreased the amount of hyperpolarization induced by aminophylline, and this is partially reversed when the xanthine concentration in the bath is increased. From the Hill equation we obtained a value of 2 for the slope, suggesting that two molecules of aminophylline bind to the receptor. Nifedipine modifies the affinity and the intrinsic activity of aminophylline, whereas verapamil reduces its intrinsic activity. The effect of nifedipine and verapamil is explained on the basis of the changed action of aminophylline on its site as a result of the interaction of the calcium channel blockers with their interdependent receptors.

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