scholarly journals Smooth muscle K-channel blocking properties of ciclazindol

1992 ◽  
Vol 58 ◽  
pp. 337
Author(s):  
T. Morita ◽  
G. Edwards ◽  
Th. Noack ◽  
P. Deitmer ◽  
A.H. Weston
Keyword(s):  
Smooth Muscle ◽  
K Channel ◽  
Channel Blocking

scholarly journals Large-conductance voltage- and Ca2+-activated K+ channel regulation by protein kinase C in guinea pig urinary bladder smooth muscle

2014 ◽  
Vol 306 (5) ◽  
pp. C460-C470 ◽  
Author(s):  
Kiril L. Hristov ◽  
Amy C. Smith ◽  
Shankar P. Parajuli ◽  
John Malysz ◽  
Georgi V. Petkov
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Guinea Pig ◽  
Bk Channels ◽  
Bk Channel ◽  
K Channel ◽  
Channel Activity ◽  
Open Probability ◽  
Channel Regulation ◽  
Pkc Activation

Large-conductance voltage- and Ca2+-activated K+ (BK) channels are critical regulators of detrusor smooth muscle (DSM) excitability and contractility. PKC modulates the contraction of DSM and BK channel activity in non-DSM cells; however, the cellular mechanism regulating the PKC-BK channel interaction in DSM remains unknown. We provide a novel mechanistic insight into BK channel regulation by PKC in DSM. We used patch-clamp electrophysiology, live-cell Ca2+ imaging, and functional studies of DSM contractility to elucidate BK channel regulation by PKC at cellular and tissue levels. Voltage-clamp experiments showed that pharmacological activation of PKC with PMA inhibited the spontaneous transient BK currents in native freshly isolated guinea pig DSM cells. Current-clamp recordings revealed that PMA significantly depolarized DSM membrane potential and inhibited the spontaneous transient hyperpolarizations in DSM cells. The PMA inhibitory effects on DSM membrane potential were completely abolished by the selective BK channel inhibitor paxilline. Activation of PKC with PMA did not affect the amplitude of the voltage-step-induced whole cell steady-state BK current or the single BK channel open probability (recorded in cell-attached mode) upon inhibition of all major Ca2+ sources for BK channel activation with thapsigargin, ryanodine, and nifedipine. PKC activation with PMA elevated intracellular Ca2+ levels in DSM cells and increased spontaneous phasic and nerve-evoked contractions of DSM isolated strips. Our results support the concept that PKC activation leads to a reduction of BK channel activity in DSM via a Ca2+-dependent mechanism, thus increasing DSM contractility.

Heterogeneous distribution of endothelium-dependent relaxations resistant to NG-nitro-L-arginine in rats

1992 ◽  
Vol 263 (4) ◽  
pp. H1090-H1094 ◽  
Author(s):  
T. Nagao ◽  
S. Illiano ◽  
P. M. Vanhoutte
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Calcium Ionophore ◽  
Renal Arteries ◽  
Mesenteric Arteries ◽  
K Channel ◽  
Ionophore A23187 ◽  
Dependent Manner ◽  
Arterial Tree ◽  
Heterogeneous Distribution

Endothelium-dependent relaxations that are resistant to inhibitors of nitric oxide synthase probably are mediated by endothelium-dependent hyperpolarization of the vascular smooth muscle. Experiments were performed to examine the distribution of this type of relaxation along the arterial tree of the rat by measuring changes in isometric force. Acetylcholine induced concentration- and endothelium-dependent relaxations in aortas and in pulmonary, common iliac, femoral, mesenteric, and renal arteries contracted with phenylephrine. In the presence of NG-nitro-L-arginine, the cumulative administration of acetylcholine induced relaxations only in the femoral, mesenteric, and renal arteries. The calcium ionophore A23187 relaxed mesenteric arteries contracted with phenylephrine in a concentration- and endothelium-dependent manner. The concentration-relaxation curve to A23187 was shifted to the right in the presence of NG-nitro-L-arginine. The maximal relaxations induced by lemakalim, a K+ channel opener, were smaller in those arteries that did not exhibit NG-nitro-L-arginine-resistant relaxations. These results suggest that NG-nitro-L-arginine-resistant relaxations are more frequently observed in smaller arteries. The arteries that exhibit NG-nitro-L-arginine-resistant relaxations may be more sensitive to an endothelium-derived substance that causes hyperpolarization of vascular smooth muscle cells.

Mechanosensitive afferents of femoral-saphenous vein

1987 ◽  
Vol 252 (2) ◽  
pp. R367-R370 ◽  
Author(s):  
P. W. Davenport ◽  
F. J. Thompson
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Contractile Response ◽  
Blocking Agent ◽  
Urotensin Ii ◽  
Dibutyryl Cyclic Amp ◽  
Maximal Contraction ◽  
Channel Blocking ◽  
Apparent Concentration ◽  
Small Contraction

Urotensin II (U II) caused marked concentration-dependent contractions of helical strips from several major arteries of the rat. The thoracic aorta was most sensitive; the apparent concentration of U II producing half-maximal contraction was 6.8 X 10(-10) M. Papaverine, dibutyryl cyclic AMP, forskolin, and nitroprusside antagonized the contractile responses to U II at the apparent concentrations producing 50% inhibition (IC50) of 7.6 X 10(-6), 2.1 X 10(-4), 2.5 X 10(-6), and 1.5 X 10(-8) M, respectively. Verapamil, a calcium channel-blocking agent, partially inhibited the contractile response to U II at IC50 = 6.5 X 10(-6) M. Maximal relaxation, i.e., a complete inhibition, could not be obtained even at a concentration of 3 X 10(-5) M verapamil. Cyproheptadine reduced the U II-induced contraction at higher concentrations. Phentolamine (10(-5) M), propranolol (10(-5) M), atropine (10(-4) M), tetrodotoxin (10(-6) M), burimamide (10(-5) M), and indomethacin (10(-5) M) did not change the U II-induced contraction. At higher concentration, U II (10(-8) M) induced a small contraction of aortic strips in Ca2+-free Krebs Henseleit solution similar to that of norepinephrine, but the U II-induced contraction was not inhibited by phentolamine or propranolol. The action of U II did not require the presence of endothelial cells. It is concluded that U II acts on vascular smooth muscle and induces the contraction partly through intracellular Ca2+ mobilization but mainly by stimulating the influx of extracellular Ca2+ via potential dependent and potential independent calcium channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Muscarinic stimulation of tracheal smooth muscle cells activates large-conductance Ca2+-dependent K+ channel

1997 ◽  
Vol 272 (3) ◽  
pp. 1-1 ◽  
Author(s):  
G. R. Wade ◽  
S. M. Sims
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Tracheal Smooth Muscle ◽  
K Channel ◽  
Muscarinic Stimulation ◽  
Cholinergic Response ◽  
Stimulation Of

Pages C658-C665: G. R. Wade and S. M. Sims. “Muscarinic stimulation of tracheal smooth muscle cells activates large-conductance Ca2+-dependent K+ channel.” Page C662, Fig. 6: the second half of the trace in A was inadvertently duplicated from B. The revised Fig. 6 below shows the correct channel traces. We wish to emphasize that the scientific point of the figure, the reversible antagonism of the cholinergic response by atropine, as well as the quantification in D, remains sound. The data were filtered at 400 Hz and sampled off-line from digital videotape at 2 kHz. (See PDF)

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