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Diabetes‐related alterations in cAMP‐mediated potassium channel currents in short term cultures of detrusor myocytes
Author(s) -
Zhao Weixin,
Brink Peter R.,
Christ George J.
Publication year - 2007
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.21.6.a829-b
Subject(s) - endocrinology , medicine , myocyte , potassium channel , apamin , streptozotocin , chemistry , diabetes mellitus , membrane potential , patch clamp , electrophysiology , biochemistry
The goal of these studies was to further explore the myogenic basis for diabetes (DM)‐related bladder dysfunction. To this end, we evaluated cAMP‐mediated K + channel function and regulation in short term cultures of detrusor myocytes derived from urothelial denuded bladders of 2‐month streptozotocin (STZ)‐diabetic (DM) and age‐matched control rats. Cell cultures (passages 1–3) were derived from male F344 rats in the following 3 groups, DM (n= 4 rats), insulin (IN)‐treated DM (n=4 rats), and an age‐matched control group (AMC; n=4 rats). Cells were voltage clamped at −70 mV and I–V curves were performed in 10 mV increments ranging from −60 mV to + 100 mV. Cells were subjected to 6 consecutive I–V curves. Following a control I–V curve, cells were exposed to the following drugs at 10–15 minute intervals: 1 mM 8‐Br‐cAMP, 100 nM IBTX (BK block), 10 μM glybenclamide (K ATP block), 100 μM 4‐AP (Kv block), and 100 nM apamin (SK block). An IN‐reversible increase in resting membrane potential, and an IN‐reversible decrease in cAMP‐induced K + currents and current density were observed (p<0.05, 2‐Way ANOVA). A significant DM‐related decline in the IBTX‐sensitive portion of the whole cell K + current, and a significant increase in the 4‐AP sensitive‐portion (p<0.05) was noted. These studies document significant DM‐related alterations in K + currents that are consistent with increased detrusor myocyte excitability (DK60037).