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.

Inhibitory Effects of Volatile Anesthetics on K+and Cl−Channel Currents in Porcine Tracheal and Bronchial Smooth Muscle

2002 ◽  
Vol 96 (2) ◽  
pp. 458-466 ◽  
Author(s):  
Xiangdong Chen ◽  
Michiaki Yamakage ◽  
Akiyoshi Namiki
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Volatile Anesthetics ◽  
Delayed Rectifier ◽  
Inhibitory Effects ◽  
Bronchial Smooth Muscle ◽  
K Channels ◽  
Channel Currents ◽  
K Currents

Background K+ and Ca2+-activated Cl- (ClCa) channel currents have been shown to contribute to the alteration of membrane electrical activity in airway smooth muscle. This study was conducted to investigate the effects of volatile anesthetics, which are potent bronchodilators, on the activities of these channels in porcine tracheal and bronchial smooth muscles. Methods Whole-cell patch clamp recording techniques were used to investigate the effects of superfused isoflurane (0-1.5 minimum alveolar concentration) or sevoflurane (0-1.5 minimum alveolar concentration) on K+ and ClCa channel currents in dispersed smooth muscle cells. Results Isoflurane and sevoflurane inhibited whole-cell K+ currents to a greater degree in tracheal versus bronchial smooth muscle cells. More than 60% of the total K+ currents in tracheal smooth muscle appeared to be mediated through delayed rectifier K+ channels compared with less than 40% in bronchial smooth muscle. The inhibitory effects of the anesthetics were greater on the delayed rectifier K+ channels than on the remaining K+ channels. Cl- currents through ClCa channels were significantly inhibited by the anesthetics. The inhibitory potencies of the anesthetics on the ClCa channels were not different in tracheal and bronchial smooth muscle cells. Conclusions Volatile anesthetics isoflurane and sevoflurane significantly inhibited Cl- currents through ClCa channels, and the inhibitory effect is consistent with the relaxant effect of volatile anesthetics in airway smooth muscle. Different distributions and different anesthetic sensitivities of K+ channel subtypes could play a role in the different inhibitory effects of the anesthetics on tracheal and bronchial smooth muscle contractions.

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.

Inhibition of voltage‐dependent K + channels by iloperidone in coronary arterial smooth muscle cells

2020 ◽  
Vol 40 (9) ◽  
pp. 1297-1305 ◽  
Author(s):  
Jin Ryeol An ◽  
Mi Seon Seo ◽  
Hee Seok Jung ◽  
Minji Kang ◽  
Ryeon Heo ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Arterial Smooth Muscle ◽  
K Channels ◽  
Voltage Dependent ◽  
Arterial Smooth Muscle Cells

Inhibitory Effects of Thiopental, Ketamine, and Propofol on Voltage-dependent Calcium sup 2+ Channels in Porcine Tracheal Smooth Muscle Cells

1995 ◽  
Vol 83 (6) ◽  
pp. 1274-1282 ◽  
Author(s):  
Michiaki Yamakage ◽  
Carol A. Hirshman ◽  
Thomas L. Croxton
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Ion Channel ◽  
Muscle Contraction ◽  
Airway Smooth Muscle ◽  
Smooth Muscle Contraction ◽  
Inhibitory Effects ◽  
Intravenous Anesthetics ◽  
Anesthetic Agents ◽  
Voltage Dependent

Abstract Background Intravenously administered anesthetics directly inhibit airway smooth muscle contraction. Because many anesthetic agents affect membrane ion channel function and sustained contraction of airway smooth muscle requires the influx of Calcium2+ through voltage-dependent Calcium2+ channels, it was hypothesized that intravenous anesthetics inhibit airway smooth muscle voltage-dependent Calcium2+ channels.

The effect of PI3 kinase inhibitor LY294002 on voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells

Life Sciences ◽  
2013 ◽  
Vol 92 (17-19) ◽  
pp. 916-922 ◽  
Author(s):  
Da Hye Hong ◽  
Il-Whan Choi ◽  
Youn Kyoung Son ◽  
Dae-Joong Kim ◽  
Sung Hun Na ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Kinase Inhibitor ◽  
Muscle Cells ◽  
Pi3 Kinase ◽  
Arterial Smooth Muscle ◽  
K Channels ◽  
Voltage Dependent ◽  
Arterial Smooth Muscle Cells

Regulation of membrane potential and diameter by voltage-dependent K+ channels in rabbit myogenic cerebral arteries

1995 ◽  
Vol 269 (1) ◽  
pp. H348-H355 ◽  
Author(s):  
H. J. Knot ◽  
M. T. Nelson
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Smooth Muscle Cells ◽  
Cerebral Arteries ◽  
Muscle Cells ◽  
Transmural Pressure ◽  
Muscle Membrane ◽  
K Channels ◽  
Wide Range ◽  
Voltage Dependent

The hypothesis that voltage-dependent K+ channels are involved in the regulation of arterial smooth muscle membrane potential and blood vessel diameter was tested by examining the effects of inhibitors [4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP)] of voltage-dependent K+ channels on the membrane potential and diameter of pressurized small (100- to 300-microns diam) cerebral arteries from rabbit. In response to graded elevations in transmural pressure (20-100 mmHg), the membrane potential of smooth muscle cells in these arteries depolarized and the arteries constricted. 4-AP (1 mM) and 3,4-DAP (1 mM) depolarized cerebral arteries by 19 and 21 mV, respectively, when they were subjected to a transmural pressure of 80 mmHg. 3-Aminopyridine (3-AP, 1 mM), which is a relatively poor inhibitor of voltage-dependent K+ channels, depolarized smooth muscle cells in the arteries by 1 mV. 4-AP and 3,4-DAP constricted pressurized (to 80 mmHg) cerebral arteries. 3-AP had little effect on arterial diameter. 4-AP increased the arterial constriction to transmural pressure over a wide range of pressures (40-90 mmHg). The effects of 4-AP and 3,4-DAP on membrane potential and diameter were not prevented by inhibitors of calcium channels, calcium-activated K+ channels, ATP-sensitive K+ channels, inward rectifier K+ channels, blockers of adrenergic, serotonergic, muscarinic, and histaminergic receptors, or removal of the endothelium. These results suggest that voltage-dependent K+ channels are involved in the regulation of membrane potential and response of small cerebral arteries to changes in intravascular pressure.

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