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Carbachol‐induced sustained tonic contraction of rat detrusor muscle
Author(s) -
SeungJune Oh,
Jung Ho Ahn,
Sung Joon Kim,
Myeong Soo Lee,
Hyung-Wook Choi
Publication year - 1999
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1046/j.1464-410x.1999.00122.x
Subject(s) - carbachol , cyclopiazonic acid , contraction (grammar) , thapsigargin , chemistry , detrusor muscle , endocrinology , medicine , muscle contraction , tonic (physiology) , ryanodine receptor , egta , extracellular , calcium , intracellular , urinary bladder , biology , biochemistry , receptor
Objective To investigate the underlying contractile mechanism of the sustained tonic contraction (SuTC) induced by repetitive carbachol application in rat detrusor muscles. Materials and methods Longitudinal muscle strips with no mucosa were obtained from the anterior wall of the urinary bladder in 12‐week‐old Sprague–Dawley rats. Carbachol (5 μmol/L) was applied repetitively to induce SuTC. The carbachol‐induced SuTC was assessed in the presence of various Ca 2+ ‐channel blockers and drugs affecting intracellular Ca 2+ concentration. Results The first application of carbachol elicited a large phasic contraction followed by a tonic contraction (TC); the carbachol‐induced contraction was completely reversed by washing out the solution. However, the initial phasic contraction was not reproduced after a second or further application of carbachol. There was consistently only a SuTC with no phasic contraction. The amplitude of the SuTC was 85% of the TC induced by the first carbachol application. The application of atropine (1 μmol/L) to the bath completely blocked SuTC. The carbachol‐induced SuTC was insensitive to nicardipine (5 μmol/L) and extracellular polyvalent cations (1 mmol/L, La 3+ , Co 2+ , Cd 2+ , Ni 2+ ). Moreover, a similar SuTC was induced even after the complete elimination of extracellular Ca 2+ by adding 2 mmol/L EGTA to the Ca 2+ ‐free Tyrode solution. To exclude intracellular Ca 2+ sources related to the sarcoplasmic reticulum (SR), the effects of SR Ca 2+ pump inhibitors, cyclopiazonic acid (CPA, 10 μmol/L) and thapsigargin (0.5 μmol/L) were tested. The carbachol‐induced SuTC was insensitive to pretreatment with CPA and/or thapsigargin. To deplete the ryanodine‐sensitive Ca 2+ pool, muscle strips were repetitively stimulated with caffeine (10 mmol/L) in the presence of 10 μmol/L ryanodine, which did not affect the carbachol‐induced SuTC. Conclusions Although the characteristics of the carbachol‐induced SuTC have not been defined, these results show that a significant proportion of the carbachol‐induced contraction in rats is contributed by the SuTC, which is present even in the complete absence of external Ca 2+ . The SuTC was not affected by limiting the contributions of internal Ca 2+ sources. This suggests that the SuTC in rat bladders is unrelated to known Ca 2+ mobilization mechanisms.