Cholesterol inhibits spontaneous action potentials and calcium currents in guinea pig gallbladder smooth muscle

1999 ◽  
Vol 277 (5) ◽  
pp. G1017-G1026 ◽  
Author(s):  
Lee J. Jennings ◽  
Qi-Wei Xu ◽  
Tracy A. Firth ◽  
Mark T. Nelson ◽  
Gary M. Mawe
Keyword(s):  
Smooth Muscle ◽  
Action Potentials ◽  
Second Messenger ◽  
Calcium Currents ◽  
Isolated Cells ◽  
Receptor Ligand ◽  
Intact Tissue ◽  
Elevated Cholesterol ◽  
Spontaneous Action ◽  
Spontaneous Action Potentials

Elevated cholesterol decreases agonist-induced contractility and enhances stone formation in the gallbladder. The current study was conducted to determine if and how the electrical properties and ionic conductances of gallbladder smooth muscle are altered by elevated cholesterol. Cholesterol was delivered as a complex with cyclodextrin, and effects were evaluated with intracellular recordings from intact gallbladder and whole cell patch-clamp recordings from isolated cells. Cholesterol significantly attenuated the spontaneous action potentials of intact tissue. Furthermore, calcium-dependent action potentials and calcium currents were reduced in the intact tissue and in isolated cells, respectively. However, neither membrane potential hyperpolarizations induced by the ATP-sensitive potassium channel opener, pinacidil, nor voltage-activated outward potassium currents were affected by cholesterol. Hyperpolarizations elicited by calcitonin gene-related peptide were reduced by cholesterol enrichment, indicating potential changes in receptor ligand binding and/or second messenger interactions. These data indicate that excess cholesterol can contribute to gallbladder stasis by affecting calcium channel activity, whereas potassium channels remained unaffected. In addition, cholesterol enrichment may also modulate receptor ligand behavior and/or second messenger interactions.

Actions of histamine on muscle and ganglia of the guinea pig gallbladder

2000 ◽  
Vol 279 (3) ◽  
pp. G622-G630 ◽  
Author(s):  
Jason M. Hemming ◽  
Fay A. Guarraci ◽  
Tracy A. Firth ◽  
Lee J. Jennings ◽  
Mark T. Nelson ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Mast Cells ◽  
Action Potentials ◽  
Resting Membrane Potential ◽  
Receptor Subtype ◽  
Excitatory Postsynaptic Potential ◽  
Membrane Hyperpolarization ◽  
Spontaneous Action ◽  
Induced Changes ◽  
Spontaneous Action Potentials

Histamine is an inflammatory mediator present in mast cells, which are abundant in the wall of the gallbladder. We examined the electrical properties of gallbladder smooth muscle and nerve associated with histamine-induced changes in gallbladder tone. Recordings were made from gallbladder smooth muscle and neurons, and responses to histamine and receptor subtype-specific compounds were tested. Histamine application to intact smooth muscle produced a concentration-dependent membrane depolarization and increased excitability. In the presence of the H2 antagonist ranitidine, the response to histamine was potentiated. Activation of H2 receptors caused membrane hyperpolarization and elimination of spontaneous action potentials. The H2response was attenuated by the ATP-sensitive K+(KATP) channel blocker glibenclamide in intact and isolated smooth muscle. Histamine had no effect on the resting membrane potential or excitability of gallbladder neurons. Furthermore, neither histamine nor the H3 agonist R-α-methylhistamine altered the amplitude of the fast excitatory postsynaptic potential in gallbladder ganglia. The mast cell degranulator compound 48/80 caused a smooth muscle depolarization that was inhibited by the H1 antagonist mepyramine, indicating that histamine released from mast cells can activate gallbladder smooth muscle. In conclusion, histamine released from mast cells can act on gallbladder smooth muscle, but not in ganglia. The depolarization and associated contraction of gallbladder smooth muscle represent the net effect of activation of both H1 (excitatory) and H2 (inhibitory) receptors, with the H2receptor-mediated response involving the activation of KATPchannels.

Vascular muscle cell depolarization and activation in renal arteries on elevation of transmural pressure

1987 ◽  
Vol 253 (4) ◽  
pp. F778-F781 ◽  
Author(s):  
D. R. Harder ◽  
R. Gilbert ◽  
J. H. Lombard
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Muscle Cell ◽  
Action Potentials ◽  
Transmural Pressure ◽  
Renal Arteries ◽  
Resting Potential ◽  
Internal Diameter ◽  
Spontaneous Action ◽  
Spontaneous Action Potentials

The goal of this study was to define some of the cellular and ionic mechanisms of smooth muscle cell activation in dog renal arteries exposed to physiological levels of transmural pressure. Isolated interlobular arteries were cannulated and connected to a pressure reservoir to allow manipulation of transmural pressure in 20-mmHg increment steps from 20 to 120 mmHg. As transmural pressure was increased, vascular smooth muscle exhibited a linear depolarization from an average resting potential of -57+/- 2 mV at 20 mmHg to -38+/- 2.4 mV at 120 mmHg. Spontaneous action potentials could often be recorded at pressures greater than 80 mmHg. These appeared to occur primarily at bifurcation points of branching arteries. Vascular smooth muscle depolarization and action potentials occurring in response to increases in transmural pressure were associated with a maintenance of internal diameter of the vessel segments despite increases in transmural pressure in the range between 60 and 120 mmHg. The “pressure-induced” activation of vascular smooth muscle contraction and spontaneous action potentials of small renal arteries at higher transmural pressures were blocked on Ca2+ channel inhibition with verapamil (10(-6) M). These data document a membrane ionic mechanism (probably increased Ca2+ influx) for pressure-induced myogenic activation of isolated renal arteries. It is interesting that the contraction of these vessels occurs over the pressure range in which autoregulation of renal blood flow normally occurs. The physiological significance of these responses needs to be determined.

Spontaneous electrical rhythmicity and the role of the sarcoplasmic reticulum in the excitability of guinea pig gallbladder smooth muscle cells

2006 ◽  
Vol 290 (4) ◽  
pp. G655-G664 ◽  
Author(s):  
Onesmo B. Balemba ◽  
Matthew J. Salter ◽  
Thomas J. Heppner ◽  
Adrian D. Bonev ◽  
Mark T. Nelson ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Action Potentials ◽  
Cyclopiazonic Acid ◽  
Cellular Mechanisms ◽  
Voltage Dependent ◽  
Spontaneous Action ◽  
Potential Activity ◽  
Spontaneous Action Potentials

Spontaneous action potentials and Ca2+ transients were investigated in intact gallbladder preparations to determine how electrical events propagate and the cellular mechanisms that modulate these events. Rhythmic phasic contractions were preceded by Ca2+ flashes that were either focal (limited to one or a few bundles), multifocal (occurring asynchronously in several bundles), or global (simultaneous flashes throughout the field). Ca2+ flashes and action potentials were abolished by inhibiting sarcoplasmic reticulum (SR) Ca2+ release via inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3] channels with 2-aminoethoxydiphenyl borate and xestospongin C or by inhibiting voltage-dependent Ca2+ channels (VDCCs) with nifedipine or diltiazem or nisoldipine. Inhibiting ryanodine channels with ryanodine caused multiple spikes superimposed upon plateaus of action potentials and extended quiescent periods. Depletion of SR Ca2+ stores with thapsigargin or cyclopiazonic acid increased the frequency and duration of Ca2+ flashes and action potentials. Acetylcholine, carbachol, or cholecystokinin increased synchronized and increased the frequency of Ca2+ flashes and action potentials. The phospholipase C (PLC) inhibitor U-73122 did not affect Ca2+ flash or action potential activity but inhibited the excitatory effects of acetylcholine on these events. These results indicate that Ca2+ flashes correspond to action potentials and that rhythmic excitation in the gallbladder is multifocal among gallbladder smooth muscle bundles and can be synchronized by excitatory agonists. These events do not depend on PLC activation, but agonist stimulation involves activation of PLC. Generation of these events depends on Ca2+ entry via VDCCs and on Ca2+ mobilization from the SR via Ins(1,4,5)P3 channels.

scholarly journals BK channel activation by NS11021 decreases excitability and contractility of urinary bladder smooth muscle

2010 ◽  
Vol 298 (2) ◽  
pp. R378-R384 ◽  
Author(s):  
Jeffrey J. Layne ◽  
Bernhard Nausch ◽  
Søren-Peter Olesen ◽  
Mark T. Nelson
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Action Potentials ◽  
Bk Channels ◽  
Bk Channel ◽  
Bladder Smooth Muscle ◽  
Open Probability ◽  
Urinary Bladder Smooth Muscle ◽  
Spontaneous Action ◽  
Spontaneous Action Potentials

Large-conductance Ca2+-activated potassium (BK) channels play an important role in regulating the function and activity of urinary bladder smooth muscle (UBSM), and the loss of BK channel function has been shown to increase UBSM excitability and contractility. However, it is not known whether activation of BK channels has the converse effect of reducing UBSM excitability and contractility. Here, we have sought to investigate this possibility by using the novel BK channel opener NS11021. NS11021 (3 μM) caused an approximately threefold increase in both single BK channel open probability ( Po) and whole cell BK channel currents. The frequency of spontaneous action potentials in UBSM strips was reduced by NS11021 from a control value of 20.9 ± 5.9 to 10.9 ± 3.7 per minute. NS11021 also reduced the force of UBSM spontaneous phasic contractions by ∼50%, and this force reduction was blocked by pretreatment with the BK channel blocker iberiotoxin. NS11021 (3 μM) had no effect on contractions evoked by nerve stimulation. These findings indicate that activating BK channels reduces the force of UBSM spontaneous phasic contractions, principally through decreasing the frequency of spontaneous action potentials.

scholarly journals Cellular Mechanisms Underlying Spontaneous Firing in Rat Suprachiasmatic Nucleus: Involvement of a Slowly Inactivating Component of Sodium Current

1997 ◽  
Vol 78 (4) ◽  
pp. 1811-1825 ◽  
Author(s):  
C.M.A. Pennartz ◽  
M. A. Bierlaagh ◽  
A.M.S. Geurtsen
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Action Potentials ◽  
Sodium Current ◽  
Calcium Currents ◽  
Spontaneous Firing ◽  
Cellular Mechanisms ◽  
Current Clamp Mode ◽  
Ionic Mechanisms ◽  
Spontaneous Action ◽  
Spontaneous Action Potentials

Pennartz, C.M.A., M. A. Bierlaagh, and A.M.S. Geurtsen. Cellular mechanisms underlying spontaneous firing in rat suprachiasmatic nucleus: involvement of a slowly inactivating component of sodium current. J. Neurophysiol. 78: 1811–1825, 1997. Neurons constituting the pacemaker of circadian rhythms, located in the suprachiasmatic nucleus, generate spontaneous firing patterns that change across the day-night cycle. Their average spontaneous firing rate is considered an important functional marker of clock activity because it is highest during daytime and low at night. In this study we investigate the ionic mechanisms underlying spontaneous firing in acutely prepared slices and dissociated neurons of the suprachiasmatic nucleus. In current-clamp mode, spontaneous action potentials were consistently preceded by depolarizing ramps. These ramps were Na+ dependent, were sensitive to tetrodotoxin (TTX), and disappeared on hyperpolarization. Ramps and associated spikes were not abolished by blockers of the H current (1 mM cesium) or calcium currents (50 μM nickel or 200 μM cadmium). In voltage-clamped neurons in slices or dissociated neurons, TTX-sensitive and Na+-dependent inward current was observed to activate well below firing threshold (−60 to −50 mV). The low-threshold component of Na+ current inactivated slowly as compared with the fast component that mediates action potentials. However, its inactivation proceeded more rapidly than has been reported for the persistent Na+ current in cortical structures. Persistent Na+ current was generally absent or small in amplitude. The voltage dependence and kinetics of the slowly inactivating component of Na+ current are consistent with the hypothesis that it is partially deinactivated during spike afterhyperpolarizations and contributes significantly to subsequent depolarizing ramps. These observations implicate the slowly inactivating component of Na+ current in ionic mechanisms governing spontaneous firing in suprachiasmatic nucleus neurons.

cAMP suppresses CA2+-dependent electrical activity of airway smooth muscle induced by TEA

1987 ◽  
Vol 62 (1) ◽  
pp. 175-179 ◽  
Author(s):  
I. S. Richards ◽  
J. Ousterhout ◽  
N. Sperelakis ◽  
C. G. Murlas
Keyword(s):  
Smooth Muscle ◽  
Electrical Activity ◽  
Airway Smooth Muscle ◽  
Action Potentials ◽  
Resting Membrane Potential ◽  
Airway Smooth Muscle Cells ◽  
Cyclic Monophosphate ◽  
Spontaneous Action ◽  
Intracellular Microelectrodes ◽  
Spontaneous Action Potentials

Using intracellular microelectrodes, we investigated whether exogenous dibutyryl adenosine 3 ′,5′-cyclic monophosphate (DBcAMP) or forskolin influenced the electrical effects of tetraethylammonium (TEA) on canine tracheal smooth muscle. We found that 20 mM TEA depolarized airway smooth muscle cells from a resting membrane potential (Em) of -59 +/- 4 mV (mean +/- SD) to -45 +/- 2 mV and caused spontaneous action potentials (AP's) to develop, which were 33 +/- 2 mV in amplitude. These were totally abolished in 0 Ca2+ solution. DBcAMP (1 mM) suppressed the development of this TEA-induced electrical activity and the phasic contractions electrically coupled to it. DBcAMP had no significant effect on Em in the absence of TEA however. Forskolin (1 microM) produced similar effects. Our findings suggest that Ca2+ is the principal ion responsible for the inward current associated with the TEA-induced AP's in airway smooth muscle, and that adenosine 3′,5′-cyclic monophosphate may suppress the electrogenesis of this current.

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