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Lookup NU author(s): Professor David Neal, Professor James Gillespie
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1 The importance of Ca2+ release from the sarcoplasmic reticulum (SR) in excitation contraction (EC) coupling in human detrusor muscle remains controversial. In this paper the contribution of Ca2+ release to agonist induced contraction is assessed. 2 Dose response curves to carbachol (0.01-10 mu M) were constructed before and after exposure to 200 nM Thapsigargin (Tg). Tg pre-treatment reduced the force of contraction at all agonist concentrations however, the reduction was dose dependent. At 0.1 mu M the contractions were reduced to 14.5 +/- 7% (mean +/- s.e.mean) of controls (n = 8) while at 10 mu M the contractions were only reduced to 92 +/- 3% of controls (n = 10). 3 The role of external Ca2+ was examined by measuring the magnitude of contraction to low and high doses of agonist in the presence and absence of external Ca2+. With (0.1-0.3 mu M) carbachol the contractions in nominally Ca2+ free media were 4 +/- 4% of controls (n = 7) whilst with (1-10 mu M) carbachol the contractions were 36 +/- 8% of controls (n = 7) suggesting that at low agonist concentrations the release of Ca2+ has a requirement for external Ca2+ 4 Pre-treatment of muscle strips with the Ca2+ channel blocking agent diltiazem reduced the contractile responses to carbachol. Contractions induced by 0.1 mu M were reduced to 29 +/- 11% (P < 0.05) of controls while those activated by 10 mu M were reduced to 86 +/- 6% (P = 0.1) of controls (n = 4) suggesting the Ca2+ influx needed to activate internal store release at low agonist stimulation is through L-type Ca2+ channels. 5 These observations confirm the importance of thapsigargin sensitive intracellular Ca2+ store release in the activation of contraction of detrusor smooth muscle and suggest the overall contribution of this store depends upon the magnitude of the agonist stimulation.
Author(s): Gillespie JI; Neal DE; Masters JG
Publication type: Article
Publication status: Published
Journal: British Journal of Pharmacology
Year: 1999
Volume: 127
Issue: 4
Pages: 996-1002
Print publication date: 01/06/1999
ISSN (print): 0007-1188
ISSN (electronic): 1476-5381
Publisher: John Wiley & Sons, Inc.
URL: http://dx.doi.org/10.1038/sj.bjp.0702640
DOI: 10.1038/sj.bjp.0702640
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