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Bladder overactivity in the streptozotocin (STZ)‐diabetic rat is associated with decreased activity of the KATP channel subtype in detrusor myocytes
Author(s) -
Jarajapu Yagna PR,
Venkateswarlu Karicheti,
Wang HongZhan,
Spektor Masha,
Zhao Weixin,
Christ George J.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1171-b
Subject(s) - glibenclamide , cystometry , endocrinology , detrusor muscle , pinacidil , medicine , carbachol , contraction (grammar) , myocyte , streptozotocin , chemistry , urinary bladder , diabetes mellitus , stimulation
The goal of these studies was to further explore the myogenic basis for diabetes (DM)‐related detrusor overactivity (DO). To this end, we evaluated K ATP channel expression and function in detrusor myocytes from DM rats. In vivo cystometry was performed in conscious, freely moving rats following 2 months of STZ‐DM. Following cystometry, urothelium denuded detrusor strips were prepared for in vitro studies. Bladder strips from DM rats showed significantly higher contractile responses to carbachol (Car) than control rats (Emax; p<0.05) with no change in sensitivity (pEC 50 ). Car‐mediated increases in intracellular calcium was higher in Fura‐2 loaded DM bladder strips (p<0.05). Attenuation and potentiation of Car‐mediated contraction by pinacidil (Pin) and glibenclamide (Glib), respectively, were significantly lower in DM bladder than in control rats (Pin: p<0.05; Glib: p<0.05). Patch clamp experiments on freshly dissociated detrusor myocytes showed reduced Glib‐sensitive outward currents to Pin in DM rats (p<0.05), and this corresponded to the reduced hyperpolarizing ability of Pin on detrusor strips from these DM rats (p<0.01). RT‐PCR assays showed no change in the mRNA expression of SUR2B in DM and control bladders. These results document a decreased K ATP channel function in DM detrusor myocytes from STZ‐DM rats with DO. (Supported by USPHS Grant DK46037).