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

Yuen Keng Ng, William C. De Groat, Hsi Yang Wu

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

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 (KCa) 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 KCa (BK) channels, or apamin (100 nM), an inhibitor of small conductance KCa (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-α mRNA increased threefold, and BK-α 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.

Original languageEnglish (US)
Pages (from-to)R2100-R2112
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume292
Issue number5
DOIs
StatePublished - May 2007
Externally publishedYes

Keywords

  • Cholinergic
  • Large-conductance K channel
  • Purinergic
  • Small-conductance K channel

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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