scholarly journals Nerve-released acetylcholine contracts urinary bladder smooth muscle by inducing action potentials independently of IP3-mediated calcium release

2010 ◽  
Vol 299 (3) ◽  
pp. R878-R888 ◽  
Author(s):  
Bernhard Nausch ◽  
Thomas J. Heppner ◽  
Mark T. Nelson
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Urinary Bladder ◽  
Action Potentials ◽  
Cyclopiazonic Acid ◽  
Electrical Field Stimulation ◽  
Field Stimulation ◽  
Bladder Smooth Muscle ◽  
Electrical Field ◽  
Urinary Bladder Smooth Muscle

Nerve-released ACh is the main stimulus for contraction of urinary bladder smooth muscle (UBSM). Here, the mechanisms by which ACh contracts UBSM are explored by determining Ca2+ and electrical signals induced by nerve-released ACh. Photolysis of caged inositol 1,4,5-trisphosphate (IP3) evoked Ca2+ release from the sarcoplasmic reticulum. Electrical field stimulation (20 Hz) induced Ca2+ waves within the smooth muscle that were present only during stimulus application. Ca2+ waves were blocked by inhibition of muscarinic ACh receptors (mAChRs) with atropine and depletion of sarcoplasmic reticulum Ca2+ stores with cyclopiazonic acid (CPA), and therefore likely reflect activation of IP3 receptors (IP3Rs). Electrical field stimulation also increased excitability to induce action potentials (APs) that were accompanied by Ca2+ flashes, reflecting Ca2+ entry through voltage-dependent Ca2+ channels (VDCCs) during the action potential. The evoked Ca2+ flashes and APs occurred as a burst with a lag time of ∼1.5 s after onset of stimulation. They were not inhibited by blocking IP3-mediated Ca2+ waves, but by blockers of mAChRs (atropine) and VDCCs (diltiazem). Nerve-evoked contractions of UBSM strips were greatly reduced by blocking VDCCs, but not by preventing IP3-mediated Ca2+ signaling with cyclopiazonic acid or inhibition of PLC with U73122. These results indicate that ACh released from nerve varicosities induces IP3-mediated Ca2+ waves during stimulation; but contrary to expectations, these signals do not appear to participate in contraction. In addition, our data provide compelling evidence that UBSM contractions evoked by nerve-released ACh depend on increased excitability and the resultant Ca2+ entry through VDCCs during APs.

scholarly journals Voltage-gated K+ channels sensitive to stromatoxin-1 regulate myogenic and neurogenic contractions of rat urinary bladder smooth muscle

2010 ◽  
Vol 299 (1) ◽  
pp. R177-R184 ◽  
Author(s):  
Muyan Chen ◽  
Whitney F. Kellett ◽  
Georgi V. Petkov
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Electrical Field Stimulation ◽  
Resting Membrane Potential ◽  
Bladder Smooth Muscle ◽  
Membrane Excitability ◽  
Molecular Fingerprints ◽  
Rat Urinary Bladder ◽  
Voltage Gated ◽  
Urinary Bladder Smooth Muscle

Members of the voltage-gated K+ (KV) channel family are suggested to control the resting membrane potential and the repolarization phase of the action potential in urinary bladder smooth muscle (UBSM). Recent studies report that stromatoxin-1, a peptide isolated from tarantulas, selectively inhibits KV2.1, KV2.2, KV4.2, and KV2.1/9.3 channels. The objective of this study was to investigate whether KV channels sensitive to stromatoxin-1 participate in the regulation of rat UBSM contractility and to identify their molecular fingerprints. Stromatoxin-1 (100 nM) increased the spontaneous phasic contraction amplitude, muscle force, and tone in isolated UBSM strips. However, stromatoxin-1 (100 nM) had no effect on the UBSM contractions induced by depolarizing agents such as KCl (20 mM) or carbachol (1 μM). This indicates that, under conditions of sustained membrane depolarization, the KV channels sensitive to stromatoxin-1 have no further contribution to the membrane excitability and contractility. Stromatoxin-1 (100 nM) increased the amplitude of the electrical field stimulation-induced contractions, suggesting also a role for these channels in neurogenic contractions. RT-PCR experiments on freshly isolated UBSM cells showed mRNA expression of KV2.1, KV2.2, and KV9.3, but not KV4.2 channel subunits. Protein expression of KV2.1 and KV2.2 channels was detected using Western blot and was further confirmed by immunocytochemical detection in freshly isolated UBSM cells. These novel findings indicate that KV2.1 and KV2.2, but not KV4.2, channel subunits are expressed in rat UBSM and play a key role in opposing both myogenic and neurogenic UBSM contractions.

The Fate of Urinary Bladder Smooth Muscle After Outlet Obstruction—A Role for the Sarcoplasmic Reticulum

2003 ◽  
pp. 773-790 ◽  
Author(s):  
Raimund Stein ◽  
ChaoLiang Gong ◽  
Joel Hutcheson ◽  
Lev Krasnopolsky ◽  
Douglas A. Canning ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Urinary Bladder ◽  
Outlet Obstruction ◽  
Bladder Smooth Muscle ◽  
Urinary Bladder Smooth Muscle

Low levels of KATP channel activation decrease excitability and contractility of urinary bladder

2001 ◽  
Vol 280 (5) ◽  
pp. R1427-R1433 ◽  
Author(s):  
Georgi V. Petkov ◽  
Thomas J. Heppner ◽  
Adrian D. Bonev ◽  
Gerald M. Herrera ◽  
Mark T. Nelson
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Action Potentials ◽  
Critical Issue ◽  
Bladder Smooth Muscle ◽  
Channel Activation ◽  
Smooth Muscle Function ◽  
Urinary Bladder Smooth Muscle ◽  
Channel Currents

Activation of ATP-sensitive potassium (KATP) channels can regulate smooth muscle function through membrane potential hyperpolarization. A critical issue in understanding the role of KATP channels is the relationship between channel activation and the effect on tissue function. Here, we explored this relationship in urinary bladder smooth muscle (UBSM) from the detrusor by activating KATP channels with the synthetic compounds N-(4-benzoylphenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide (ZD-6169) and levcromakalim. The effects of ZD-6169 and levcromakalim on KATP channel currents in isolated UBSM cells, on action potentials, and on related phasic contractions of isolated UBSM strips were examined. ZD-6169 and levcromakalim at 1.02 and 2.63 μM, respectively, caused half-maximal activation (K1/2) of KATP currents in single UBSM cells (see Heppner TJ, Bonev A, Li JH, Kau ST, and Nelson MT. Pharmacology 53: 170–179, 1996). In contrast, much lower concentrations (K1/2 = 47 nM for ZD-6169 and K1/2 = 38 nM for levcromakalim) caused inhibition of action potentials and phasic contractions of UBSM. The results suggest that activation of <1% of KATP channels is sufficient to inhibit significantly action potentials and the related phasic contractions.

scholarly journals Small-conductance, Ca2+-activated K+ channel 2 is the key functional component of SK channels in mouse urinary bladder

2008 ◽  
Vol 294 (5) ◽  
pp. R1737-R1743 ◽  
Author(s):  
K. S. Thorneloe ◽  
A. M. Knorn ◽  
P. E. Doetsch ◽  
E. S. R. Lashinger ◽  
A. X. Liu ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Action Potentials ◽  
Electrical Field Stimulation ◽  
K Channel ◽  
Sk Channels ◽  
Bladder Smooth Muscle ◽  
Sk Channel ◽  
Urinary Bladder Smooth Muscle ◽  
Insight Into ◽  
Small Conductance

Small-conductance Ca2+-activated K+ (SK) channels play an important role in regulating the frequency and in shaping urinary bladder smooth muscle (UBSM) action potentials, thereby modulating contractility. Here we investigated a role for the SK2 member of the SK family (SK1-3) utilizing: 1) mice expressing β-galactosidase (β-gal) under the direction of the SK2 promoter (SK2 β-gal mice) to localize SK2 expression and 2) mice lacking SK2 gene expression (SK2−/− mice) to assess SK2 function. In SK2 β-gal mice, UBSM staining was observed, but staining was undetected in the urothelium. Consistent with this, urothelial SK2 mRNA was determined to be 4% of that in UBSM. Spontaneous phasic contractions in wild-type (SK2+/+) UBSM strips were potentiated (259% of control) by the selective SK channel blocker apamin (EC50 = 0.16 nM), whereas phasic contractions of SK2−/− strips were unaffected. Nerve-mediated contractions of SK2+/+ UBSM strips were also increased by apamin, an effect absent in SK2−/− strips. Apamin increased the sensitivity of SK2+/+ UBSM strips to electrical field stimulation, since pretreatment with apamin decreased the frequency required to reach a 50% maximal contraction (vehicle, 21 ± 4 Hz, n = 6; apamin, 12 ± 2 Hz, n = 7; P < 0.05). In contrast, the sensitivity of SK2−/− UBSM strips was unaffected by apamin. Here we provide novel insight into the molecular basis of SK channels in the urinary bladder, demonstrating that the SK2 gene is expressed in the bladder and that it is essential for the ability of SK channels to regulate UBSM contractility.

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.

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