title: Phasic activity of urinary bladder smooth muscle in the streptozotocin-induced diabetic rat: effect of potassium channel modulators.
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 BKCa 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 KATP 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 BKCa 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 SKCa and KATP channels did not induce phasic activity in resting tissues. In conclusion, responses of diabetic rat bladder to BKCa and KATP channel modulators are altered, suggesting altered function and/or expression of channels which may contribute to bladder dysfunction in this model.
authors.affiliation: Biomedical Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UK. bahareh.vahabi@uwe.ac.uk
authors.forename: Bahareh
authors.initials: B
authors.lastname: Vahabi
authors.forename: Kim
authors.initials: K
authors.lastname: Lawson
authors.forename: Neil G
authors.initials: NG
authors.lastname: McKay
authors.forename: Donna J
authors.initials: DJ
authors.lastname: Sellers
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D001562:Benzimidazoles; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019806:Cromakalim; C086491:NS 1619