Trimebutine maleate has inhibitory effects on the voltage-dependent Ca2+ inward current and other membrane currents in intestinal smooth muscle cells

1990 ◽  
Vol 25 (2) ◽  
pp. 175-179 ◽  
Author(s):  
Tadahito Shimada ◽  
Yoshihisa Kurachi ◽  
Akira Terano ◽  
Eiji Hamada ◽  
Tsuneaki Sugimoto
1989 ◽  
Vol 414 (4) ◽  
pp. 401-409 ◽  
Author(s):  
M. Yoshino ◽  
T. Someya ◽  
A. Nishio ◽  
K. Yazawa ◽  
T. Usuki ◽  
...  

2001 ◽  
Vol 94 (4) ◽  
pp. 683-693 ◽  
Author(s):  
Michiaki Yamakage ◽  
Xiangdong Chen ◽  
Naoki Tsujiguchi ◽  
Yasuhiro Kamada ◽  
Akiyoshi Namiki

Background The distal airway is more important in the regulation of airflow resistance than is the proximal airway, and volatile anesthetics have a greater inhibitory effect on distal airway muscle tone. The authors investigated the different reactivities of airway smooth muscles to volatile anesthetics by measuring porcine tracheal or bronchial (third to fifth generation) smooth muscle tension and intracellular concentration of free Ca2+ ([Ca2+]i) and by measuring inward Ca2+ currents (ICa) through voltage-dependent Ca2+ channels (VDCs). Methods Intracellular concentration of free Ca2+ was monitored by the 500-nm light emission ratio of Ca2+ indicator fura-2. Isometric tension was measured simultaneously. Whole-cell patch clamp recording techniques were used to investigate the effects of volatile anesthetics on ICa in dispersed smooth muscle cells. Isoflurane (0-1.5 minimum alveolar concentration) or sevoflurane (0-1.5 minimum alveolar concentration) was introduced into a bath solution. Results The volatile anesthetics tested had greater inhibitory effects on carbachol-induced bronchial smooth muscle contraction than on tracheal smooth muscle contraction. These inhibitory effects by the anesthetics on muscle tension were parallel to the inhibitory effects on [Ca2+]i. Although tracheal smooth muscle cells had only L-type VDCs, some bronchial smooth muscle cells (approximately 30%) included T-type VDC. Each of the two anesthetics significantly inhibited the activities of both types of VDCs in a dose-dependent manner; however, the anesthetics had greater inhibitory effects on T-type VDC activity in bronchial smooth muscle. Conclusions The existence of the T-type VDC in bronchial smooth muscle and the high sensitivity of this channel to volatile anesthetics seem to be, at least in part, responsible for the different reactivities to the anesthetics in tracheal and bronchial smooth muscles.


2000 ◽  
Vol 528 (3) ◽  
pp. 521-537 ◽  
Author(s):  
A. V. Zholos ◽  
C. J. Fenech ◽  
S. A. Prestwich ◽  
T. B. Bolton

1990 ◽  
Vol 258 (5) ◽  
pp. G794-G802 ◽  
Author(s):  
S. M. Sims ◽  
M. B. Vivaudou ◽  
C. Hillemeier ◽  
P. Biancani ◽  
J. V. Walsh ◽  
...  

The tight-seal whole cell recording technique with patch pipettes was used to study membrane currents of smooth muscle cells freshly dissociated from the esophagus of cats. Under voltage clamp with K+ in the pipette, depolarizing commands elicited an initial inward current followed by a transient outward current that peaked and then declined to reveal spontaneous outward currents (SOCs). SOCs were evident at -60 mV and more positive potentials. The reversal of SOCs at the K+ equilibrium potential and their suppression by tetraethylammonium chloride lead to the conclusion that they represent the activity of K+ channels. Acetylcholine (ACh) caused reversible contraction of these cells and had two successive effects on membrane currents, causing transient activation of K+ current followed by suppression of SOCs. Both of these effects were blocked by atropine. Consistent with these observations, in current clamp, ACh caused a transient hyperpolarization followed by depolarization. The inward current activated by depolarization was blocked by external Cd2+, consistent with the inward current being a voltage-activated calcium current. Two types of Ca2+ current could be distinguished on the basis of voltage-activation range, time course of inactivation and "run-down" during whole cell recording.


1993 ◽  
Vol 264 (2) ◽  
pp. C296-C301 ◽  
Author(s):  
K. Obara ◽  
H. Yabu

The effects of okadaic acid (OA) and calyculin A (CL-A), potent inhibitors of protein phosphatases type 1 (PP1) and type 2A (PP2A), on inward current carried by Ba2+ through voltage-dependent Ca2+ channel in guinea pig teniae coli smooth muscle cells were investigated using whole-cell patch-clamp technique. High concentrations of OA (5 x 10(-8)-5 x 10(-6) M) and CL-A (10(-9)-10(-7) M) dose dependently increased the inward current. The concentration producing apparent half-maximum enhancing effect values for OA and CL-A were 1.12 x 10(-7) and 1.78 x 10(-9) M, respectively. CL-A appeared to be approximately 100-fold more potent in increasing the inward current than OA. Lower concentrations of OA (10(-10)-2 x 10(-8) M) and CL-A (10(-11)-10(-9) M) decreased the inward current. The maximum inhibitory effects of OA and CL-A were observed at 10(-8) M OA and 5 x 10(-10) M CL-A, respectively. CL-A is approximately 100 times more effective inhibitor of PP1 than OA, and lower concentrations of OA and CL-A used in the present study inhibit PP2A activity, but they have no or little effect on PP1 activity (Ishihara, H., B. L. Martin, D. L. Brautigan, H. Karaki, H. Ozaki, Y. Kato, N. Fusetani, S. Watabe, K. Hashimoto, D. Uemura and D. J. Hartshorne. Biochem. Biophys. Res. Commun. 159: 871-877, 1989). In the absence of ATP in pipette solution, OA and CL-A did not affect the inward current.(ABSTRACT TRUNCATED AT 250 WORDS)


1991 ◽  
Vol 47 (9) ◽  
pp. 939-941 ◽  
Author(s):  
T. Usuki ◽  
K. Obara ◽  
T. Someya ◽  
H. Ozaki ◽  
H. Karaki ◽  
...  

1999 ◽  
Vol 90 (1) ◽  
pp. 197-207 ◽  
Author(s):  
Michiaki Yamakage ◽  
Takashi Matsuzaki ◽  
Naoki Tsujiguchi ◽  
Yasuyuki Honma ◽  
Akiyoshi Namiki

Background Benzodiazepines have a direct bronchodilator action in airway smooth muscle, but the mechanisms by which these agents produce muscle relaxation are not fully understood. The current study was performed to identify the effects of the benzodiazepines diazepam and midazolam on Ca2+ and K+ channels in canine tracheal smooth muscle cells. Methods Whole-cell patch-clamp recording techniques were used to evaluate the effects of the benzodiazepines diazepam (10(-8) to 10(-3) M) and midazolam (10(-8) to 10(-3) M) on inward Ca2+ and outward K+ channel currents in dispersed canine tracheal smooth muscle cells. The effects of the antagonists flumazenil (10(-5) M) and PK11195 (10(-5) M) on these channels were also studied. Results Each benzodiazepine tested significantly inhibited Ca2+ currents in a dose-dependent manner, with 10(-6) M diazepam and 10(-5) M midazolam each causing approximately 50% depression of peak voltage-dependent Ca2+ currents. Both benzodiazepines promoted the inactivated state of the channel at more-negative potentials. The Ca2+-activated and voltage-dependent K+ currents were inhibited by diazepam and midazolam (> 10(-5) M and > 10(-4) M, respectively). Flumazenil and PK11195 had no effect on these channel currents or on the inhibitory effects of the benzodiazepines. Conclusions Diazepam and midazolam had inhibitory effects on voltage-dependent Ca2+ channels, which lead to muscle relaxation. However, high concentrations of these agents were necessary to inhibit the K+ channels. The lack of antagonized effects of their antagonists is related to the non-gamma-aminobutyric acid-mediated electrophysiologic effects of benzodiazepines on airway smooth muscle contractility.


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