Skip to main content
Erschienen in: International Urology and Nephrology 1/2017

14.11.2016 | Urology - Original Paper

Partial bladder outlet obstruction is associated with decreased expression and function of the small-conductance Ca2+-activated K+ channel in guinea pig detrusor smooth muscle

verfasst von: Ning Li, Xiaoning He, Zizheng Li, Yili Liu, Ping Wang

Erschienen in: International Urology and Nephrology | Ausgabe 1/2017

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Partial bladder outlet obstruction (PBOO) usually induces overactive bladder (OAB) associated with detrusor overactivity (DO) which is related to the increased contractility of detrusor smooth muscle (DSM). The pharmacological activation of small-conductance Ca2+-activated K+ (SK) channels dramatically attenuates DSM contractility. However, the role of SK channels in the PBOO DSM is less clear. Here, we tested the hypothesis that PBOO is associated with decreased expression and function of SK channels in DSM and that the activation of SK channels is a potential target to regulate DO.

Methods

Two weeks after surgically inducing PBOO in female guinea pigs, cystometry indicated that DO was achieved. Using this animal model, we conducted quantitative reverse transcription–polymerase chain reaction (qRT-PCR) and isometric tension recordings.

Results

The qRT-PCR experiments indicated that PBOO DSM had reduced SK channel mRNA expression. Isometric tension recordings showed a decreased inhibitory effect of NS309 on spontaneous phasic and electrical field stimulation-induced contractions via the activation of SK channels in PBOO DSM.

Conclusions

This study presents the novel finding that PBOO is associated with attenuated DSM SK channel expression and function, which results in increased DSM contractility and contributes to DO. Therefore, SK channels could be a therapeutic target to control OAB.
Literatur
1.
Zurück zum Zitat Berry SJ, Coffey DS, Walsh PC, Ewing LL (1984) The development of human benign prostatic hyperplasia with age. J Urol 132(3):474–479PubMed Berry SJ, Coffey DS, Walsh PC, Ewing LL (1984) The development of human benign prostatic hyperplasia with age. J Urol 132(3):474–479PubMed
2.
Zurück zum Zitat Andersson KE (2003) Storage and voiding symptoms: pathophysiologic aspects. Urology 62(5 Suppl 2):3–10CrossRefPubMed Andersson KE (2003) Storage and voiding symptoms: pathophysiologic aspects. Urology 62(5 Suppl 2):3–10CrossRefPubMed
3.
Zurück zum Zitat Oelke M, Baard J, Wijkstra H, de la Rosette JJ, Jonas U, Hofner K (2008) Age and bladder outlet obstruction are independently associated with detrusor overactivity in patients with benign prostatic hyperplasia. Eur Urol 54(2):419–426. doi:10.1016/j.eururo.2008.02.017 CrossRefPubMed Oelke M, Baard J, Wijkstra H, de la Rosette JJ, Jonas U, Hofner K (2008) Age and bladder outlet obstruction are independently associated with detrusor overactivity in patients with benign prostatic hyperplasia. Eur Urol 54(2):419–426. doi:10.​1016/​j.​eururo.​2008.​02.​017 CrossRefPubMed
4.
Zurück zum Zitat Bing W, Chang S, Hypolite JA, DiSanto ME, Zderic SA, Rolf L, Wein AJ, Chacko S (2003) Obstruction-induced changes in urinary bladder smooth muscle contractility: a role for Rho kinase. Am J Physiol Renal Physiol 285(5):F990–F997. doi:10.1152/ajprenal.00378.2002 CrossRefPubMed Bing W, Chang S, Hypolite JA, DiSanto ME, Zderic SA, Rolf L, Wein AJ, Chacko S (2003) Obstruction-induced changes in urinary bladder smooth muscle contractility: a role for Rho kinase. Am J Physiol Renal Physiol 285(5):F990–F997. doi:10.​1152/​ajprenal.​00378.​2002 CrossRefPubMed
5.
Zurück zum Zitat DiSanto ME, Stein R, Chang S, Hypolite JA, Zheng Y, Zderic S, Wein AJ, Chacko S (2003) Alteration in expression of myosin isoforms in detrusor smooth muscle following bladder outlet obstruction. Am J Physiol Cell Physiol 285(6):C1397–C1410. doi:10.1152/ajpcell.00513.2002 CrossRefPubMed DiSanto ME, Stein R, Chang S, Hypolite JA, Zheng Y, Zderic S, Wein AJ, Chacko S (2003) Alteration in expression of myosin isoforms in detrusor smooth muscle following bladder outlet obstruction. Am J Physiol Cell Physiol 285(6):C1397–C1410. doi:10.​1152/​ajpcell.​00513.​2002 CrossRefPubMed
9.
Zurück zum Zitat Parajuli SP, Soder RP, Hristov KL, Petkov GV (2012) Pharmacological activation of small conductance calcium-activated potassium channels with naphtho[1,2-d]thiazol-2-ylamine decreases guinea pig detrusor smooth muscle excitability and contractility. J Pharmacol Exp Ther 340(1):114–123. doi:10.1124/jpet.111.186213 CrossRefPubMedPubMedCentral Parajuli SP, Soder RP, Hristov KL, Petkov GV (2012) Pharmacological activation of small conductance calcium-activated potassium channels with naphtho[1,2-d]thiazol-2-ylamine decreases guinea pig detrusor smooth muscle excitability and contractility. J Pharmacol Exp Ther 340(1):114–123. doi:10.​1124/​jpet.​111.​186213 CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Chang S, Gomes CM, Hypolite JA, Marx J, Alanzi J, Zderic SA, Malkowicz B, Wein AJ, Chacko S (2010) Detrusor overactivity is associated with downregulation of large-conductance calcium- and voltage-activated potassium channel protein. Am J Physiol Ren Physiol 298(6):F1416–F1423. doi:10.1152/ajprenal.00595.2009 CrossRef Chang S, Gomes CM, Hypolite JA, Marx J, Alanzi J, Zderic SA, Malkowicz B, Wein AJ, Chacko S (2010) Detrusor overactivity is associated with downregulation of large-conductance calcium- and voltage-activated potassium channel protein. Am J Physiol Ren Physiol 298(6):F1416–F1423. doi:10.​1152/​ajprenal.​00595.​2009 CrossRef
12.
Zurück zum Zitat Aydin M, Wang HZ, Zhang X, Chua R, Downing K, Melman A, DiSanto ME (2012) Large-conductance calcium-activated potassium channel activity, as determined by whole-cell patch clamp recording, is decreased in urinary bladder smooth muscle cells from male rats with partial urethral obstruction. BJU Int 110((8 Pt B)):402–408. doi:10.1111/j.1464-410X.2012.11137.x CrossRef Aydin M, Wang HZ, Zhang X, Chua R, Downing K, Melman A, DiSanto ME (2012) Large-conductance calcium-activated potassium channel activity, as determined by whole-cell patch clamp recording, is decreased in urinary bladder smooth muscle cells from male rats with partial urethral obstruction. BJU Int 110((8 Pt B)):402–408. doi:10.​1111/​j.​1464-410X.​2012.​11137.​x CrossRef
14.
16.
Zurück zum Zitat Herrera GM, Heppner TJ, Nelson MT (2000) Regulation of urinary bladder smooth muscle contractions by ryanodine receptors and BK and SK channels. Am J Physiol Regul Integr Comp Physiol 279(1):R60–R68PubMed Herrera GM, Heppner TJ, Nelson MT (2000) Regulation of urinary bladder smooth muscle contractions by ryanodine receptors and BK and SK channels. Am J Physiol Regul Integr Comp Physiol 279(1):R60–R68PubMed
17.
Zurück zum Zitat Hashitani H, Brading AF, Suzuki H (2004) Correlation between spontaneous electrical, calcium and mechanical activity in detrusor smooth muscle of the guinea-pig bladder. Br J Pharmacol 141(1):183–193. doi:10.1038/sj.bjp.0705602 CrossRefPubMed Hashitani H, Brading AF, Suzuki H (2004) Correlation between spontaneous electrical, calcium and mechanical activity in detrusor smooth muscle of the guinea-pig bladder. Br J Pharmacol 141(1):183–193. doi:10.​1038/​sj.​bjp.​0705602 CrossRefPubMed
18.
Zurück zum Zitat Thorneloe KS, Knorn AM, Doetsch PE, Lashinger ES, Liu AX, Bond CT, Adelman JP, Nelson MT (2008) Small-conductance, Ca2+ -activated K+ channel 2 is the key functional component of SK channels in mouse urinary bladder. Am J Physiol Regul Integr Comp Physiol 294(5):R1737–R1743. doi:10.1152/ajpregu.00840.2006 CrossRefPubMedPubMedCentral Thorneloe KS, Knorn AM, Doetsch PE, Lashinger ES, Liu AX, Bond CT, Adelman JP, Nelson MT (2008) Small-conductance, Ca2+ -activated K+ channel 2 is the key functional component of SK channels in mouse urinary bladder. Am J Physiol Regul Integr Comp Physiol 294(5):R1737–R1743. doi:10.​1152/​ajpregu.​00840.​2006 CrossRefPubMedPubMedCentral
21.
23.
Zurück zum Zitat Kaiho Y, Nishiguchi J, Kwon DD, Chancellor MB, Arai Y, Snyder PB, Yoshimura N (2008) The effects of a type 4 phosphodiesterase inhibitor and the muscarinic cholinergic antagonist tolterodine tartrate on detrusor overactivity in female rats with bladder outlet obstruction. BJU Int 101(5):615–620. doi:10.1111/j.1464-410X.2007.07307.x CrossRefPubMed Kaiho Y, Nishiguchi J, Kwon DD, Chancellor MB, Arai Y, Snyder PB, Yoshimura N (2008) The effects of a type 4 phosphodiesterase inhibitor and the muscarinic cholinergic antagonist tolterodine tartrate on detrusor overactivity in female rats with bladder outlet obstruction. BJU Int 101(5):615–620. doi:10.​1111/​j.​1464-410X.​2007.​07307.​x CrossRefPubMed
25.
Zurück zum Zitat Gui L, LaGrange LP, Larson RA, Gu M, Zhu J, Chen QH (2012) Role of small conductance calcium-activated potassium channels expressed in PVN in regulating sympathetic nerve activity and arterial blood pressure in rats. Am J Physiol Regul Integr Comp Physiol 303(3):R301–R310. doi:10.1152/ajpregu.00114.2012 CrossRefPubMedPubMedCentral Gui L, LaGrange LP, Larson RA, Gu M, Zhu J, Chen QH (2012) Role of small conductance calcium-activated potassium channels expressed in PVN in regulating sympathetic nerve activity and arterial blood pressure in rats. Am J Physiol Regul Integr Comp Physiol 303(3):R301–R310. doi:10.​1152/​ajpregu.​00114.​2012 CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3(6):1101–1108CrossRefPubMed Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3(6):1101–1108CrossRefPubMed
27.
Zurück zum Zitat Kubota Y, Hashitani H, Shirasawa N, Kojima Y, Sasaki S, Mabuchi Y, Soji T, Suzuki H, Kohri K (2008) Altered distribution of interstitial cells in the guinea pig bladder following bladder outlet obstruction. Neurourol Urodyn 27(4):330–340. doi:10.1002/nau.20502 CrossRefPubMed Kubota Y, Hashitani H, Shirasawa N, Kojima Y, Sasaki S, Mabuchi Y, Soji T, Suzuki H, Kohri K (2008) Altered distribution of interstitial cells in the guinea pig bladder following bladder outlet obstruction. Neurourol Urodyn 27(4):330–340. doi:10.​1002/​nau.​20502 CrossRefPubMed
29.
Zurück zum Zitat Soder RP, Parajuli SP, Hristov KL, Rovner ES, Petkov GV (2013) SK channel-selective opening by SKA-31 induces hyperpolarization and decreases contractility in human urinary bladder smooth muscle. Am J Physiol Regul Integr Comp Physiol 304(2):R155–R163. doi:10.1152/ajpregu.00363.2012 CrossRefPubMed Soder RP, Parajuli SP, Hristov KL, Rovner ES, Petkov GV (2013) SK channel-selective opening by SKA-31 induces hyperpolarization and decreases contractility in human urinary bladder smooth muscle. Am J Physiol Regul Integr Comp Physiol 304(2):R155–R163. doi:10.​1152/​ajpregu.​00363.​2012 CrossRefPubMed
31.
Zurück zum Zitat Wolffenbuttel KP, Kok DJ, Minekus JP, van Koeveringe GA, van Mastrigt R, Nijman JM (2001) Urodynamic follow-up of experimental urethral obstruction in individual guinea pigs. Neurourol Urodyn 20(6):699–713CrossRefPubMed Wolffenbuttel KP, Kok DJ, Minekus JP, van Koeveringe GA, van Mastrigt R, Nijman JM (2001) Urodynamic follow-up of experimental urethral obstruction in individual guinea pigs. Neurourol Urodyn 20(6):699–713CrossRefPubMed
34.
Zurück zum Zitat Brading AF (1997) A myogenic basis for the overactive bladder. Urology 50(6A Suppl):57–67 (discussion 68–73) CrossRefPubMed Brading AF (1997) A myogenic basis for the overactive bladder. Urology 50(6A Suppl):57–67 (discussion 68–73) CrossRefPubMed
35.
Zurück zum Zitat de Groat WC (1997) A neurologic basis for the overactive bladder. Urology 50(6A Suppl):36–52 (discussion 53–36) CrossRefPubMed de Groat WC (1997) A neurologic basis for the overactive bladder. Urology 50(6A Suppl):36–52 (discussion 53–36) CrossRefPubMed
Metadaten
Titel
Partial bladder outlet obstruction is associated with decreased expression and function of the small-conductance Ca2+-activated K+ channel in guinea pig detrusor smooth muscle
verfasst von
Ning Li
Xiaoning He
Zizheng Li
Yili Liu
Ping Wang
Publikationsdatum
14.11.2016
Verlag
Springer Netherlands
Erschienen in
International Urology and Nephrology / Ausgabe 1/2017
Print ISSN: 0301-1623
Elektronische ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-016-1455-0

Weitere Artikel der Ausgabe 1/2017

International Urology and Nephrology 1/2017 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.