scholarly journals Nerve-evoked purinergic signalling suppresses action potentials, Ca2+flashes and contractility evoked by muscarinic receptor activation in mouse urinary bladder smooth muscle

2009 ◽  
Vol 587 (21) ◽  
pp. 5275-5288 ◽  
Author(s):  
Thomas J. Heppner ◽  
Matthias E. Werner ◽  
Bernhard Nausch ◽  
Catherine Vial ◽  
Richard J. Evans ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Muscarinic Receptor ◽  
Action Potentials ◽  
Receptor Activation ◽  
Purinergic Signalling ◽  
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 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 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 Stretch-induced Calcium Release in Smooth Muscle

2002 ◽  
Vol 119 (6) ◽  
pp. 533-543 ◽  
Author(s):  
Guangju Ji ◽  
Robert J. Barsotti ◽  
Morris E. Feldman ◽  
Michael I. Kotlikoff
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Smooth Muscle Cells ◽  
Calcium Release ◽  
Muscle Cells ◽  
Intraluminal Pressure ◽  
Bladder Smooth Muscle ◽  
Urinary Bladder Smooth Muscle ◽  
Inward Currents ◽  
Longitudinal Stretch

Smooth muscle cells undergo substantial increases in length, passively stretching during increases in intraluminal pressure in vessels and hollow organs. Active contractile responses to counteract increased transmural pressure were first described almost a century ago (Bayliss, 1902) and several mechanisms have been advanced to explain this phenomenon. We report here that elongation of smooth muscle cells results in ryanodine receptor–mediated Ca2+ release in individual myocytes. Mechanical elongation of isolated, single urinary bladder myocytes to ∼120% of slack length (ΔL = 20) evoked Ca2+ release from intracellular stores in the form of single Ca2+ sparks and propagated Ca2+ waves. Ca2+ release was not due to calcium-induced calcium release, as release was observed in Ca2+-free extracellular solution and when free Ca2+ ions in the cytosol were strongly buffered to prevent increases in [Ca2+]i. Stretch-induced calcium release (SICR) was not affected by inhibition of InsP3R-mediated Ca2+ release, but was completely blocked by ryanodine. Release occurred in the absence of previously reported stretch-activated currents; however, SICR evoked calcium-activated chloride currents in the form of transient inward currents, suggesting a regulatory mechanism for the generation of spontaneous currents in smooth muscle. SICR was also observed in individual myocytes during stretch of intact urinary bladder smooth muscle segments. Thus, longitudinal stretch of smooth muscle cells induces Ca2+ release through gating of RYR. SICR may be an important component of the physiological response to increases in luminal pressure in smooth muscle tissues.

In vitro and in vivo relaxation of urinary bladder smooth muscle by the selective myosin II inhibitor, blebbistatin

2011 ◽  
Vol 107 (2) ◽  
pp. 310-317 ◽  
Author(s):  
Xinhua Zhang ◽  
Dwaraka Srinivasa R. Kuppam ◽  
Arnold Melman ◽  
Michael E. DiSanto
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Myosin Ii ◽  
Bladder Smooth Muscle ◽  
Urinary Bladder Smooth Muscle
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