Effects of K + channel openers on spontaneous action potentials in detrusor smooth muscle of the guinea-pig urinary bladder

2016 ◽  
Vol 789 ◽  
pp. 179-186 ◽  
Author(s):  
Hiroaki Takagi ◽  
Hikaru Hashitani
2010 ◽  
Vol 298 (2) ◽  
pp. R378-R384 ◽  
Author(s):  
Jeffrey J. Layne ◽  
Bernhard Nausch ◽  
Søren-Peter Olesen ◽  
Mark T. Nelson

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.


The effects of incubation conditions on the frequency of spontaneous action potentials exhibited by guinea-pig cerebellar slices, and recorded with an extracellular microelectrode, have been investigated. Various incubation conditions that lead to tetrodotoxin-sensitive uptakes of water and of sodium ions by the incubated cerebellar slices lead to enhanced frequencies of the spontaneous action potentials, e. g. the presence of protoveratrine or of ouabain, the absence of glucose or the onset of anoxia. The frequency of the spikes is also enhanced by acetylcholine (in presence of neostigmine) or by the presence of excitatory amino acids, such as L-glutamate, D-glutamate or L-aspartate. It is suppressed by tetrodotoxin, or by the inhibitory amino acids, e. g. γ -aminobutyrate, glycine or taurine, or by ammonium ions or by pentobarbital. It is concluded that guinea-pig cerebellar slices, incubated under specified conditions, may provide a suitable means for quantitative correlation of neurochemical data with data obtained by electrophysiological techniques in tissue incubated under similar conditions and also for quantitative assessment of the effects of amino acids on cerebellar electrical activity.


2000 ◽  
Vol 279 (3) ◽  
pp. G622-G630 ◽  
Author(s):  
Jason M. Hemming ◽  
Fay A. Guarraci ◽  
Tracy A. Firth ◽  
Lee J. Jennings ◽  
Mark T. Nelson ◽  
...  

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.


1999 ◽  
Vol 277 (5) ◽  
pp. G1017-G1026 ◽  
Author(s):  
Lee J. Jennings ◽  
Qi-Wei Xu ◽  
Tracy A. Firth ◽  
Mark T. Nelson ◽  
Gary M. Mawe

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.


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