Relaxant effects of potassium-channel openers on normal and hyper-reflexic detrusor muscle

S. W. Martin, S. C. Radley, R. Chess-Williams, C. Korstanjet, C. R. Chapple

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Abstract

Objective: To compare the effects of the potassium-channel openers, levcromakalim and YM934, in isolated human detrusor muscle from normal and hyper-reflexic bladders. Materials and methods: Strips of human detrusor muscle from normal and hyper-reflexic bladder were precontracted with carbachol and the potassium-channel openers (0.1-0.3 μmol/L) were added cumulatively to the organ baths. Other strips were field-stimulated at frequencies producing 25% and 75% of the maximum response to field stimulation. Contractions could be abolished by atropine (10 μmol/L) and tetrodotoxin (1 μmol/L). Results: The hyper-reflexic bladder was significantly more sensitive to carbachol than the normal bladder but the maximum response was significantly lower in the hyper-reflexic tissue. There was no significant difference between the potency of the potassium-channel openers in normal and hyper-reflexic detrusor muscle. Hyper-reflexic bladder was significantly more sensitive to electrical field stimulation than was normal bladder; maximum responses to field stimulation were not significantly different. Concentration-response curves for the potassium-channel openers were displaced to the left in hyper-reflexic bladder at both 25% and 75% maximum frequencies; however, only with levcromakalim at 75% of the maximum frequency was the shift significant. Conclusion: The greater sensitivity of hyper-reflexic bladder to carbachol and field stimulation supports existing evidence for post-junctional supersensitivity in detrusor instability. The results of this study also suggest that there are no appreciable changes in K(ATP) channel function in the unstable bladder.

Original languageEnglish
Pages (from-to)405-413
Number of pages9
JournalBritish Journal of Urology
Volume80
Issue number3
DOIs
Publication statusPublished - 1 Dec 1997
Externally publishedYes

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Potassium Channels
Urinary Bladder
Muscles
Carbachol
Cromakalim
Tetrodotoxin
Baths
Atropine
Electric Stimulation
Adenosine Triphosphate

Cite this

Martin, S. W. ; Radley, S. C. ; Chess-Williams, R. ; Korstanjet, C. ; Chapple, C. R. / Relaxant effects of potassium-channel openers on normal and hyper-reflexic detrusor muscle. In: British Journal of Urology. 1997 ; Vol. 80, No. 3. pp. 405-413.
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abstract = "Objective: To compare the effects of the potassium-channel openers, levcromakalim and YM934, in isolated human detrusor muscle from normal and hyper-reflexic bladders. Materials and methods: Strips of human detrusor muscle from normal and hyper-reflexic bladder were precontracted with carbachol and the potassium-channel openers (0.1-0.3 μmol/L) were added cumulatively to the organ baths. Other strips were field-stimulated at frequencies producing 25{\%} and 75{\%} of the maximum response to field stimulation. Contractions could be abolished by atropine (10 μmol/L) and tetrodotoxin (1 μmol/L). Results: The hyper-reflexic bladder was significantly more sensitive to carbachol than the normal bladder but the maximum response was significantly lower in the hyper-reflexic tissue. There was no significant difference between the potency of the potassium-channel openers in normal and hyper-reflexic detrusor muscle. Hyper-reflexic bladder was significantly more sensitive to electrical field stimulation than was normal bladder; maximum responses to field stimulation were not significantly different. Concentration-response curves for the potassium-channel openers were displaced to the left in hyper-reflexic bladder at both 25{\%} and 75{\%} maximum frequencies; however, only with levcromakalim at 75{\%} of the maximum frequency was the shift significant. Conclusion: The greater sensitivity of hyper-reflexic bladder to carbachol and field stimulation supports existing evidence for post-junctional supersensitivity in detrusor instability. The results of this study also suggest that there are no appreciable changes in K(ATP) channel function in the unstable bladder.",
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Relaxant effects of potassium-channel openers on normal and hyper-reflexic detrusor muscle. / Martin, S. W.; Radley, S. C.; Chess-Williams, R.; Korstanjet, C.; Chapple, C. R.

In: British Journal of Urology, Vol. 80, No. 3, 01.12.1997, p. 405-413.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Martin, S. W.

AU - Radley, S. C.

AU - Chess-Williams, R.

AU - Korstanjet, C.

AU - Chapple, C. R.

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N2 - Objective: To compare the effects of the potassium-channel openers, levcromakalim and YM934, in isolated human detrusor muscle from normal and hyper-reflexic bladders. Materials and methods: Strips of human detrusor muscle from normal and hyper-reflexic bladder were precontracted with carbachol and the potassium-channel openers (0.1-0.3 μmol/L) were added cumulatively to the organ baths. Other strips were field-stimulated at frequencies producing 25% and 75% of the maximum response to field stimulation. Contractions could be abolished by atropine (10 μmol/L) and tetrodotoxin (1 μmol/L). Results: The hyper-reflexic bladder was significantly more sensitive to carbachol than the normal bladder but the maximum response was significantly lower in the hyper-reflexic tissue. There was no significant difference between the potency of the potassium-channel openers in normal and hyper-reflexic detrusor muscle. Hyper-reflexic bladder was significantly more sensitive to electrical field stimulation than was normal bladder; maximum responses to field stimulation were not significantly different. Concentration-response curves for the potassium-channel openers were displaced to the left in hyper-reflexic bladder at both 25% and 75% maximum frequencies; however, only with levcromakalim at 75% of the maximum frequency was the shift significant. Conclusion: The greater sensitivity of hyper-reflexic bladder to carbachol and field stimulation supports existing evidence for post-junctional supersensitivity in detrusor instability. The results of this study also suggest that there are no appreciable changes in K(ATP) channel function in the unstable bladder.

AB - Objective: To compare the effects of the potassium-channel openers, levcromakalim and YM934, in isolated human detrusor muscle from normal and hyper-reflexic bladders. Materials and methods: Strips of human detrusor muscle from normal and hyper-reflexic bladder were precontracted with carbachol and the potassium-channel openers (0.1-0.3 μmol/L) were added cumulatively to the organ baths. Other strips were field-stimulated at frequencies producing 25% and 75% of the maximum response to field stimulation. Contractions could be abolished by atropine (10 μmol/L) and tetrodotoxin (1 μmol/L). Results: The hyper-reflexic bladder was significantly more sensitive to carbachol than the normal bladder but the maximum response was significantly lower in the hyper-reflexic tissue. There was no significant difference between the potency of the potassium-channel openers in normal and hyper-reflexic detrusor muscle. Hyper-reflexic bladder was significantly more sensitive to electrical field stimulation than was normal bladder; maximum responses to field stimulation were not significantly different. Concentration-response curves for the potassium-channel openers were displaced to the left in hyper-reflexic bladder at both 25% and 75% maximum frequencies; however, only with levcromakalim at 75% of the maximum frequency was the shift significant. Conclusion: The greater sensitivity of hyper-reflexic bladder to carbachol and field stimulation supports existing evidence for post-junctional supersensitivity in detrusor instability. The results of this study also suggest that there are no appreciable changes in K(ATP) channel function in the unstable bladder.

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