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 journalArticlepeer-review

80 Citations (Scopus)


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
Issue number2
Publication statusPublished - Aug 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Urology


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