A1115 The Inhibitory Effects of Benzodiazepines on Voltage-dependent Ca sup 2+ and K sup + Channels in Canine Tracheal Smooth Muscle Cells

1997 ◽  
Vol 87 (Supplement) ◽  
pp. 1115A
Author(s):  
M. Yamakage ◽  
&NA; Matsuzaki T. ◽  
Y. Honma ◽  
H. Iwasaki ◽  
A. Namiki
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Tracheal Smooth Muscle ◽  
Inhibitory Effects ◽  
Voltage Dependent

Inhibitory Effects of Diazepam and Midazolam on Ca2+and K+Channels in Canine Tracheal Smooth Muscle Cells 

1999 ◽  
Vol 90 (1) ◽  
pp. 197-207 ◽  
Author(s):  
Michiaki Yamakage ◽  
Takashi Matsuzaki ◽  
Naoki Tsujiguchi ◽  
Yasuyuki Honma ◽  
Akiyoshi Namiki
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Muscle Relaxation ◽  
Muscle Cells ◽  
Tracheal Smooth Muscle ◽  
Inhibitory Effects ◽  
K Channels ◽  
Voltage Dependent ◽  
Channel Currents

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.

ω-3 Polyunsaturated fatty acids—modulation of voltage-dependent L-type Ca2+ current in guinea-pig tracheal smooth muscle cells

1998 ◽  
Vol 355 (2-3) ◽  
pp. 257-266 ◽  
Author(s):  
Hisanori Hazama ◽  
Toshiaki Nakajima ◽  
Michiko Asano ◽  
Kuniaki Iwasawa ◽  
Toshihiro Morita ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Smooth Muscle ◽  
Guinea Pig ◽  
Polyunsaturated Fatty Acids ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Tracheal Smooth Muscle ◽  
Voltage Dependent

Different Inhibitory Effects of Volatile Anesthetics on T- and L-type Voltage-dependent Ca2+Channels in Porcine Tracheal and Bronchial Smooth Muscles

2001 ◽  
Vol 94 (4) ◽  
pp. 683-693 ◽  
Author(s):  
Michiaki Yamakage ◽  
Xiangdong Chen ◽  
Naoki Tsujiguchi ◽  
Yasuhiro Kamada ◽  
Akiyoshi Namiki
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Tension ◽  
Smooth Muscles ◽  
Muscle Cells ◽  
Volatile Anesthetics ◽  
Smooth Muscle Contraction ◽  
Inhibitory Effects ◽  
Bronchial Smooth Muscle ◽  
Voltage Dependent

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.

Intracellular pH regulates voltage-dependent Ca2+ channels in porcine tracheal smooth muscle cells

1995 ◽  
Vol 268 (4) ◽  
pp. L642-L646 ◽  
Author(s):  
M. Yamakage ◽  
K. S. Lindeman ◽  
C. A. Hirshman ◽  
T. L. Croxton
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Tracheal Smooth Muscle ◽  
Airway Smooth Muscle Cells ◽  
Smooth Muscle Contractility ◽  
Voltage Dependent ◽  
Airway Tone ◽  
Ca2 Channels

Changes in CO2 or in pH modify airway smooth muscle contractility. To investigate the mechanisms involved, we compared K(+)-induced contractions in porcine bronchial rings exposed to different CO2 concentrations and directly measured the effects of changes in intracellular (pHi) or extracellular pH (pHo) on Ca2+ currents (ICa) through voltage-dependent Ca2+ channels (VDC) in porcine tracheal smooth muscle cells. Hypocapnia and hypercapnia caused leftward and rightward shifts, respectively, in the dose-response to K+ (P < 0.05) but did not change the maximum force obtained. Peak ICa (10 mM external Ca2+) elicited by depolarizing pulses from -80 mV was maximal [-265 +/- 12 pA (mean +/- SE), n = 19] at +10 mV. Intracellular acidification decreased the peak ICa at +10 mV from -261 +/- 20 pA to -177 +/- 12 pA (P < 0.05, n = 4), while intracellular alkalinization increased the peak ICa at +10 mV from -302 +/- 27 pA to -368 +/- 26 pA (P < 0.05, n = 4). Changes in pHo had little effect on ICa. There was no shift in the voltage-dependence of induced ICa with any change. We conclude that pHi, but not pHo, directly modulates the entry of Ca2+ into airway smooth muscle cells through VDC. This mechanism may contribute to regulation of airway tone by CO2.

Cholinergic regulation of voltage-dependent Ca2+ channels in porcine tracheal smooth muscle cells

1995 ◽  
Vol 269 (6) ◽  
pp. L776-L782 ◽  
Author(s):  
M. Yamakage ◽  
C. A. Hirshman ◽  
T. L. Croxton
Keyword(s):  
Smooth Muscle ◽  
Charge Carrier ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Tracheal Smooth Muscle ◽  
Whole Cell ◽  
Cholinergic Regulation ◽  
Voltage Dependent ◽  
Inward Currents ◽  
Ca2 Channels

To investigate cholinergic regulation of voltage-dependent Ca2+ channels (VDCs) in airway smooth muscle, we measured inward currents through VDCs in enzymatically dispersed porcine tracheal smooth muscle cells using conventional (10 mM Ca2+ as charge carrier) and nystatin-perforated (5 mM Ba2+ as charge carrier) whole cell patch clamp techniques. Carbachol (CCh) had significant and dose-dependent inhibitory effects on inward currents (12% with 10(-7) M and 42% with 10(-6) M) in perforated whole cell clamp experiments, but had no effect on currents in conventional whole cell experiments. CCh also shifted the steady-state inactivation curve to more negative potentials. Further experiments tested the hypothesis that CCh inhibits VDCs in part by the activation of protein kinase C (PKC). Phorbol 12,13-diacetate, an exogenous PKC activator, inhibited currents through VDCs. and calphostin C, a specific PKC inhibitor, antagonized the inhibitory effect of CCh. Furthermore, intracellular exposure to the activating PKC fragment 530-558, using a pipette perfusion technique, also inhibited currents through VDCs. We conclude that cholinergic receptor stimulation can inhibit inward Ca2+ currents through VDCs of porcine tracheal smooth muscle and that this effect may be mediated in part by activation of PKC.

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