Physiological significance of hyperpolarization-activated inward currents (I h) in smooth muscle cells from the circular layers of pregnant rat myometrium

1999 ◽  
Vol 439 (1) ◽  
pp. 76-85 ◽  
Author(s):  
K. Okabe ◽  
Y. Inoue ◽  
T. Kawarabayashi ◽  
H. Kajiya ◽  
F. Okamoto ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Physiological Significance ◽  
Pregnant Rat ◽  
Inward Currents

scholarly journals Stretch-induced Calcium Release in Smooth Muscle

2002 ◽  
Vol 119 (6) ◽  
pp. 533-543 ◽  
Author(s):  
Guangju Ji ◽  
Robert J. Barsotti ◽  
Morris E. Feldman ◽  
Michael I. Kotlikoff
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Smooth Muscle Cells ◽  
Calcium Release ◽  
Muscle Cells ◽  
Intraluminal Pressure ◽  
Bladder Smooth Muscle ◽  
Urinary Bladder Smooth Muscle ◽  
Inward Currents ◽  
Longitudinal Stretch

Smooth muscle cells undergo substantial increases in length, passively stretching during increases in intraluminal pressure in vessels and hollow organs. Active contractile responses to counteract increased transmural pressure were first described almost a century ago (Bayliss, 1902) and several mechanisms have been advanced to explain this phenomenon. We report here that elongation of smooth muscle cells results in ryanodine receptor–mediated Ca2+ release in individual myocytes. Mechanical elongation of isolated, single urinary bladder myocytes to ∼120% of slack length (ΔL = 20) evoked Ca2+ release from intracellular stores in the form of single Ca2+ sparks and propagated Ca2+ waves. Ca2+ release was not due to calcium-induced calcium release, as release was observed in Ca2+-free extracellular solution and when free Ca2+ ions in the cytosol were strongly buffered to prevent increases in [Ca2+]i. Stretch-induced calcium release (SICR) was not affected by inhibition of InsP3R-mediated Ca2+ release, but was completely blocked by ryanodine. Release occurred in the absence of previously reported stretch-activated currents; however, SICR evoked calcium-activated chloride currents in the form of transient inward currents, suggesting a regulatory mechanism for the generation of spontaneous currents in smooth muscle. SICR was also observed in individual myocytes during stretch of intact urinary bladder smooth muscle segments. Thus, longitudinal stretch of smooth muscle cells induces Ca2+ release through gating of RYR. SICR may be an important component of the physiological response to increases in luminal pressure in smooth muscle tissues.

An ATP-sensitive conductance in cultured smooth muscle cells from pregnant rat myometrium

1989 ◽  
Vol 257 (2) ◽  
pp. C297-C305 ◽  
Author(s):  
E. Honore ◽  
C. Martin ◽  
C. Mironneau ◽  
J. Mironneau
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Voltage Clamp ◽  
Free Acid ◽  
Muscle Cells ◽  
Monovalent Cation ◽  
Acid Form ◽  
Pregnant Rat ◽  
Free Acid Form ◽  
Cultured Smooth Muscle Cells

The whole cell voltage-clamp technique was used to study the effects of extracellular ATP in cultured smooth muscle cells isolated from pregnant rat myometrium. An inward current was elicited by ATP (IATP) in cells held at -70 mV under voltage clamp. The amplitude of IATP was reduced by estrogen pretreatment and by the end of pregnancy. IATP not only did not undergo any desensitization but showed facilitation. The current-voltage relationship of IATP was linear and reversed close to 0 mV. Changing the sodium electrochemical gradient by decreasing extracellular or intracellular sodium resulted in a linear relationship between the reversal potential of IATP and Na equilibrium potential that, however, differed from the predicted curve for a purely sodium conductance. The conductance activated by ATP was monovalent cation selective with little discrimination between potassium, cesium, and sodium ions. IATP was depressed by divalent cations, and the rank order of potency was Co greater than Mg greater than Ca greater than Ba, suggesting that the free-acid form of ATP was the effective ligand. Adenosine, AMP, and ADP were ineffective in eliciting IATP, whereas ATP gamma S and alpha,beta-methylene ATP were capable of mimicking the effects of ATP, although they were less potent. These results are consistent with the free-acid form of ATP activating a monovalent cation-selective and estrogen-sensitive conductance in myometrium.

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.

Fast Na+ channels in smooth muscle from pregnant rat uterus

1992 ◽  
Vol 70 (4) ◽  
pp. 491-500 ◽  
Author(s):  
Nicholas Sperelakis ◽  
Yoshihito Inoue ◽  
Yusuke Ohya
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Current Density ◽  
Sodium Current ◽  
Muscle Cells ◽  
Slow Inward Current ◽  
Rat Uterus ◽  
Pregnant Rat ◽  
Inward Current ◽  
Channel Current

Smooth muscle cells normally do not possess fast Na+ channels, but inward current is carried through two types of Ca2+ channels: slow (L type) Ca2+ channels and fast (T type) Ca2+ channels. Whole-cell voltage clamp was done on single smooth muscle cells isolated from the longitudinal layer of the 18-day pregnant rat uterus. Depolarizing pulses, applied from a holding potential of −90 mV, evoked two types of inward current, fast and slow. The fast inward current decayed within 30 ms, depended on [Na]o, and was inhibited by tetrodotoxin (TTX) (K0.5 = 27 nM). The slow inward current decayed slowly, was dependent on [Ca]o (or Ba2+), and was inhibited by nifedipine. These results suggest that the fast inward current is a fast Na+ channel current and that the slow inward current is a Ca2+ slow channel current. A fast-inactivating Ca2+ channel current was not evident. We conclude that the ion channels that generate inward currents in pregnant rat uterine cells are TTX-sensitive fast Na+ channels and dihydropyridine-sensitive slow Ca2+ channels. The number of fast Na+ channels increased during gestation. The averaged current density increased from 0 on day 5, to 0.19 on day 9, to 0.56 on day 14, to 0.90 on day 18, and to 0.86 pA/pF on day 21. This almost linear increase occurs because of an increase in the fraction of cells that possess fast Na+ channels. The Ca2+ channel current density was also higher during the latter half of gestation. These results indicate that the fast Na+ channels and Ca2+ slow channels in myometrium become more numerous as term approaches, and we suggest that the fast Na+ current may be involved in spread of excitation. Isoproterenol (β-agonist) did not affect either ICa(s) or INa(f), whereas Mg2+ (K0.5 = 12 mM) and nifedipine (K0.5 = 3.3 nM) depressed ICa(s). Oxytocin had no effect on INa(f) and actually depressed ICa(s) to a small extent. Therefore, the tocolytic action of β-agonists cannot be explained by an inhibition of ICa(s), whereas that of Mg2+ can be so explained. The stimulating action of oxytocin on uterine contractions cannot be explained by a stimulation of ICa(s).Key words: sodium current, fast sodium current, calcium currents, myometrial smooth muscle cells, pregnant uterine muscle.

Gestational change in Na+ and Ca2+ channel current densities in rat myometrial smooth muscle cells

1991 ◽  
Vol 260 (3) ◽  
pp. C658-C663 ◽  
Author(s):  
Y. Inoue ◽  
N. Sperelakis
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Reversal Potential ◽  
Cell Voltage ◽  
Muscle Cells ◽  
Linear Increase ◽  
Na Channels ◽  
Pregnant Rat ◽  
Spread Of Excitation ◽  
Current Densities

The change of Na+ and Ca2+ channel currents during gestation was investigated using the whole cell voltage-clamp method on single smooth muscle cells freshly isolated from the longitudinal layer of pregnant rat uterus. The current-voltage relationships for both the Na+ and Ca2+ currents did not change during gestation. The threshold voltage, the voltage at the peak inward current, and the reversal potential (extrapolated) were virtually identical. The averaged current densities of Ca2+ channel were almost unchanged between days 9 and 21; this value at day 5 was somewhat lower. In contrast, the averaged current density of fast Na+ channels increased markedly in the myometrium during gestation: from 0 at day 5 to 0.19 +/- 0.16 at day 9, to 0.56 +/- 0.13 at day 14, to 0.90 +/- 0.13 at day 18, and to 0.86 +/- 0.14 pA/pF at day 21. This almost linear increase in the averaged density of fast Na+ channels during gestation occurs because of an increase in the fraction of cells which possessed fast Na+ channels. These results suggest that the role of fast Na+ channels in myometrial activity becomes more and more important as term approaches. We suggest that the fast Na+ current may be involved in spread of excitation.

Forskolin inhibition of K+ current in pregnant rat uterine smooth muscle cells

1993 ◽  
Vol 240 (2-3) ◽  
pp. 169-176 ◽  
Author(s):  
Yoshihito Inoue ◽  
Keiichi Shimamura ◽  
Nicholas Sperelakis
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Pregnant Rat ◽  
Uterine Smooth Muscle ◽  
K Current

scholarly journals Functional characterization of voltage-dependent Ca2+ channels in mouse pulmonary arterial smooth muscle cells: divergent effect of ROS

2013 ◽  
Vol 304 (11) ◽  
pp. C1042-C1052 ◽  
Author(s):  
Eun A. Ko ◽  
Jun Wan ◽  
Aya Yamamura ◽  
Adriana M. Zimnicka ◽  
Hisao Yamamura ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Function ◽  
Electromechanical Coupling ◽  
Functional Characterization ◽  
Muscle Cells ◽  
Pulmonary Vascular Disease ◽  
High K ◽  
Voltage Dependent ◽  
Inward Currents

Electromechanical coupling via membrane depolarization-mediated activation of voltage-dependent Ca2+ channels (VDCC) is an important mechanism in regulating pulmonary vascular tone, while mouse is an animal model often used to study pathogenic mechanisms of pulmonary vascular disease. The function of VDCC in mouse pulmonary artery (PA) smooth muscle cells (PASMC), however, has not been characterized, and their functional role in reactive oxygen species (ROS)-mediated regulation of vascular function remains unclear. In this study, we characterized the electrophysiological and pharmacological properties of VDCC in PASMC and the divergent effects of ROS produced by xanthine oxidase (XO) and hypoxanthine (HX) on VDCC in PA and mesenteric artery (MA). Our data show that removal of extracellular Ca2+ or application of nifedipine, a dihydropyridine VDCC blocker, both significantly inhibited 80 mM K+-mediated PA contraction. In freshly dissociated PASMC, the maximum inward Ca2+ currents were −2.6 ± 0.2 pA/pF at +10 mV (with a holding potential of −70 mV). Window currents were between −40 and +10 mV with a peak at −15.4 mV. Nifedipine inhibited currents with an IC50 of 0.023 μM, and 1 μM Bay K8644, a dihydropyridine VDCC agonist, increased the inward currents by 61%. XO/HX attenuated 60 mM K+-mediated increase in cytosolic free Ca2+ concentration ([Ca2+]cyt) due to Ca2+ influx through VDCC in PASMC. Exposure to XO/HX caused relaxation in PA preconstricted by 80 mM K+ but not in aorta and MA. In contrast, H2O2 inhibited high K+-mediated increase in [Ca2+]cyt and caused relaxation in both PA and MA. Indeed, RT-PCR and Western blot analysis revealed significantly lower expression of CaV1.3 in MA compared with PA. Thus our study characterized the properties of VDCC and demonstrates that ROS differentially regulate vascular contraction by regulating VDCC in PA and systemic arteries.

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