Ca2+ sensitization in contraction of human urinary bladder smooth muscle

Ryosuke Takahashi, Narihito Seki, Nobuyuki Kai, Hiroshi Seguchi, Seiji Naito

Research output: Contribution to journalArticle

Abstract

The role of Ca2+ sensitization in the contraction of human urinary bladder smooth muscle (UBSM) was investigated. 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. The expressions of proteins were confirmed by western blot analysis. 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 a constant [Ca2+]i and produced a leftward shift in the [Ca2+]i-tension relationship. RhoA, Rho-associated kinase (ROCK) I, ROCKII and CPI-17 proteins were expressed in human UBSM. In intact fura-2 loaded strips, application of 3 μM Y-27632 (a ROCK inhibitor) or 3 μM GF109203X (a protein kinase C (PKC) inhibitor) during the sustained phase of contraction induced by 1 μM CCh induced a relaxation without changing [Ca2+]i. In α-toxin permeabilized strips, application of 3 μM Y-27632 or 3 μM GF109203X during the sustained contraction induced by 0.3 μM Ca2+ plus 10 M GTP and 1 μM CCh induced a relaxation at constant [Ca2+]i. These results indicate that in human UBSM, CCh induces a contraction not only by increasing [Ca2+]i but also by increasing the Ca2+ sensitivity of the contractile apparatus in a ROCK-and PKC-dependent manner. Antagonism of Ca2+ sensitization pathways may represent an alternative target in the treatment of overactive bladder.

Original languageEnglish
Pages (from-to)232-237
Number of pages6
JournalNishinihon Journal of Urology
Volume67
Issue number5
Publication statusPublished - May 1 2005

All Science Journal Classification (ASJC) codes

  • Urology

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    Takahashi, R., Seki, N., Kai, N., Seguchi, H., & Naito, S. (2005). Ca2+ sensitization in contraction of human urinary bladder smooth muscle. Nishinihon Journal of Urology, 67(5), 232-237.