Smooth muscle and neural mechanisms contributing to the downregulation of neonatal rat spontaneous bladder contractions during postnatal development

1 Department of Surgery, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; 2 Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania; and 3 Department of Pediatric Urology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania Submitted 8 November 2006 ; accepted in final form 16 January 2007 Spontaneous bladder contractions (SBCs) in the neonatal rat urinary bladder change from a high-amplitude, low-frequency pattern to a low-amplitude, high-frequency pattern during the first 6 wk of life. Understanding the mechanism of this developmental change may provide insights into the causes of bladder overactivity in adults. In vitro whole bladder preparations from Sprague-Dawley rats were used to study the modulation of SBCs by calcium-activated potassium channels (K Ca ) and electrical field stimulation from 3 days to 6 wk of life. SBCs in 3-day-old bladders were unmasked by treatment with iberiotoxin (100 nM), an inhibitor of large conductance K Ca (BK) channels, or apamin (100 nM), an inhibitor of small conductance K Ca (SK) channels. Iberiotoxin significantly increased the magnitude of SBCs at 2–3 wk, whereas apamin was only effective at 6 wk. In 1–2 wk bladders, exposure to room temperature Krebs solution decreased SBCs. This decrease was reversed by activating intramural nerves with electrical field stimulation. The effect of electrical field stimulation was inhibited by atropine (1 µM), suramin (10 µM), or pretreatment with tetrodotoxin (1 µM) but was not reversed by tetrodotoxin applied after electrical field stimulation. BK- mRNA increased threefold, and BK- protein increased fivefold from 3 days to 6 wk. These data suggest that BK channels play an important role in the regulation of SBCs in the neonatal bladder and that both increased BK channel activity, as well as changes in smooth muscle sensitivity to locally released neurotransmitters contribute to the downregulation of SBCs during early postnatal development. large-conductance K Ca channel; small-conductance K Ca channel; cholinergic; purinergic Address for reprint requests and other correspondence: Hsi-Yang Wu, Dept. of Pediatric Urology, G205 DeSoto, Children's Hospital of Pittsburgh, 3705 Fifth Ave., Pittsburgh, PA 15213 (e-mail: wuhy{at}chp.edu )