Phasic activity of urinary bladder smooth muscle in the streptozotocin-induced diabetic rat: Effect of potassium channel modulators

Bahareh Vahabi, Kim Lawson, Neil G. McKay, Donna J. Sellers

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10 Citations (Scopus)

Abstract

Increased phasic activity in the bladder smooth muscle of animal models and patients with detrusor overactivity has been suggested to underlie the pathophysiology of overactive bladder. Potassium (K +) channels are key regulators of bladder smooth muscle tone and thus may play a role in this altered phasic activity. In this study the effects of K + channel modulators on the phasic activity of bladder strips from the streptozotocin-induced diabetic rat model of bladder dysfunction were investigated. Bladder strips from rats 1 week following streptozotocin administration and age-matched controls were mounted in tissue baths at 37 °C and the effects of K + channel modulators on resting basal tension or phasic activity induced by a low concentration of carbachol (0.5 μM) were investigated. Activation of BK Ca channels by NS1619 had a minor inhibitory effect on carbachol-induced phasic activity of bladder strips from control and diabetic rats, and significantly inhibited amplitude only at 30 μM. Activation of K ATP channels by cromakalim inhibited the frequency of carbachol-induced phasic activity of bladder strips, although strips from diabetic rats showed a trend towards being less sensitive to cromakalim. The BK Ca channel blocker iberiotoxin was able to induce phasic activity in resting tissues, with diabetic bladder strips demonstrating significantly enhanced phasic activity compared to controls. In contrast, inhibition of SK Ca and K ATP channels did not induce phasic activity in resting tissues. In conclusion, responses of diabetic rat bladder to BK Ca and K ATP channel modulators are altered, suggesting altered function and/or expression of channels which may contribute to bladder dysfunction in this model.

Original languageEnglish
Pages (from-to)431-437
Number of pages7
JournalEuropean Journal of Pharmacology
Volume660
Issue number2-3
DOIs
Publication statusPublished - 25 Jun 2011

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Potassium Channels
Streptozocin
Smooth Muscle
Urinary Bladder
Carbachol
Cromakalim
Large-Conductance Calcium-Activated Potassium Channels
Adenosine Triphosphate
Overactive Urinary Bladder
Baths
Animal Models

Cite this

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abstract = "Increased phasic activity in the bladder smooth muscle of animal models and patients with detrusor overactivity has been suggested to underlie the pathophysiology of overactive bladder. Potassium (K +) channels are key regulators of bladder smooth muscle tone and thus may play a role in this altered phasic activity. In this study the effects of K + channel modulators on the phasic activity of bladder strips from the streptozotocin-induced diabetic rat model of bladder dysfunction were investigated. Bladder strips from rats 1 week following streptozotocin administration and age-matched controls were mounted in tissue baths at 37 °C and the effects of K + channel modulators on resting basal tension or phasic activity induced by a low concentration of carbachol (0.5 μM) were investigated. Activation of BK Ca channels by NS1619 had a minor inhibitory effect on carbachol-induced phasic activity of bladder strips from control and diabetic rats, and significantly inhibited amplitude only at 30 μM. Activation of K ATP channels by cromakalim inhibited the frequency of carbachol-induced phasic activity of bladder strips, although strips from diabetic rats showed a trend towards being less sensitive to cromakalim. The BK Ca channel blocker iberiotoxin was able to induce phasic activity in resting tissues, with diabetic bladder strips demonstrating significantly enhanced phasic activity compared to controls. In contrast, inhibition of SK Ca and K ATP channels did not induce phasic activity in resting tissues. In conclusion, responses of diabetic rat bladder to BK Ca and K ATP channel modulators are altered, suggesting altered function and/or expression of channels which may contribute to bladder dysfunction in this model.",
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Phasic activity of urinary bladder smooth muscle in the streptozotocin-induced diabetic rat : Effect of potassium channel modulators. / Vahabi, Bahareh; Lawson, Kim; McKay, Neil G.; Sellers, Donna J.

In: European Journal of Pharmacology, Vol. 660, No. 2-3, 25.06.2011, p. 431-437.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Sellers, Donna J.

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