Ca2+ sensitization in contraction of human bladder smooth muscle

Ryosuke Takahashi, Junji Nishimura, Katsuya Hirano, Narihito Seki, Seiji Naito, Hideo Kanaide

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Purpose: The role of Ca2+ sensitization in the contraction of human bladder urinary smooth muscle (UBSM) was investigated. Materials and Methods: Simultaneous measurements of intracellular Ca2+ concentration ([Ca2+]i) and tension in fura-2 loaded intact strips and receptor coupled strips permeabilized with α-toxin were applied. Protein expressions was confirmed by Western blot analysis. Results: In intact fura-2 loaded strips 1 μM carbachol (CCh) induced a greater contraction and a lower [Ca2+]i elevation than that induced by 60 mM K+ depolarization. In α-toxin permeabilized strips 1 μM CCh induced contraction at constant [Ca2+]i and produced a leftward shift in the [Ca2+]i-tension relationship. RhoA, Rho-associated kinase (ROCK) I, ROCK II and CPI-17 proteins were expressed in human UBSM. In intact fura-2 loaded strips the application of 3 μM Y-27632, a ROCK inhibitor, or 3 μM bisindolylmaleimide I (GF109203X), a protein kinase C inhibitor, during the sustained phase of contraction induced by 1 μM CCh induced relaxation without changing [Ca2+] i. In α-toxin permeabilized strips the application of 3 μM Y-27632 or 3 μM GF109203X during the sustained contraction induced by 0.3 μM Ca2+ plus 10 μM guanosine triphosphate and 1 μM CCh induced relaxation at constant [Ca2+]i. Conclusions: These results indicate that in human UBSM CCh induces contraction, not only by increasing [Ca2+]i, but also by increasing the Ca 2+ sensitivity of the contractile apparatus in a ROCK and protein kinase C dependent manner. Antagonism of Ca2+ sensitization pathways may represent an alternative target in the treatment of overactive bladder.

Original languageEnglish
Pages (from-to)748-752
Number of pages5
JournalJournal of Urology
Volume172
Issue number2
DOIs
Publication statusPublished - Jan 1 2004

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Carbachol
rho-Associated Kinases
Smooth Muscle
Urinary Bladder
Fura-2
Protein Kinase C
Overactive Urinary Bladder
Protein C Inhibitor
Protein Kinase Inhibitors
Guanosine Triphosphate
Proteins
Western Blotting
bisindolylmaleimide I
Y 27632

All Science Journal Classification (ASJC) codes

  • Urology

Cite this

Takahashi, R., Nishimura, J., Hirano, K., Seki, N., Naito, S., & Kanaide, H. (2004). Ca2+ sensitization in contraction of human bladder smooth muscle. Journal of Urology, 172(2), 748-752. https://doi.org/10.1097/01.ju.0000130419.32165.6b

Ca2+ sensitization in contraction of human bladder smooth muscle. / Takahashi, Ryosuke; Nishimura, Junji; Hirano, Katsuya; Seki, Narihito; Naito, Seiji; Kanaide, Hideo.

In: Journal of Urology, Vol. 172, No. 2, 01.01.2004, p. 748-752.

Research output: Contribution to journalArticle

Takahashi, R, Nishimura, J, Hirano, K, Seki, N, Naito, S & Kanaide, H 2004, 'Ca2+ sensitization in contraction of human bladder smooth muscle', Journal of Urology, vol. 172, no. 2, pp. 748-752. https://doi.org/10.1097/01.ju.0000130419.32165.6b
Takahashi R, Nishimura J, Hirano K, Seki N, Naito S, Kanaide H. Ca2+ sensitization in contraction of human bladder smooth muscle. Journal of Urology. 2004 Jan 1;172(2):748-752. https://doi.org/10.1097/01.ju.0000130419.32165.6b
Takahashi, Ryosuke ; Nishimura, Junji ; Hirano, Katsuya ; Seki, Narihito ; Naito, Seiji ; Kanaide, Hideo. / Ca2+ sensitization in contraction of human bladder smooth muscle. In: Journal of Urology. 2004 ; Vol. 172, No. 2. pp. 748-752.
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