Intracellular calcium mobilization of the aganglionic intestine in the endothelin B receptor gene -deficient rat

Takanori Nakatsuji, Satoshi Ieiri, Kouji Masumoto, Junko Akiyoshi, Tomoaki Taguchi, Sachiyo Suita

研究成果: ジャーナルへの寄稿学術誌査読

9 被引用数 (Scopus)


Background and Aim: Up to now, numerous reports have analyzed the pathogenesis of Hirschsprung's disease (HD) by means of physiologic, pathologic, or molecular biologic methods. However, very little is still known about the smooth muscle cell itself. The endothelin B receptor gene-deficient (EDNRB(-/-)) rat, which is suitable for research of HD, has an aganglionic segment of the total colon. Our purpose is to investigate the myogenic mechanisms using simultaneous measurements of the intracellular Ca2+ concentration ([Ca2+]i) and tension and reverse transcriptase polymerase chain reaction for L-type Ca2+ channel (L-VOC) expression. Methods: The muscle strips of the rat distal colon were loaded with a Ca2+ indicator dye, fura-PE3/AM, for 3 to 4 hours. The changes in the fluorescence intensity of Ca2+-fura-PE3 complex of the strips were monitored with a front surface fluorometer (CAM-230). The fluorescence intensities at 340- and 380-nm excitation and their ratio (F340/F380) were recorded as the level of [Ca2+]i. The comparison of L-VOC α1c subunit messenger RNA (mRNA) expression in both wild and homozygous rat was performed by reverse transcriptase polymerase chain reaction. Results: The peak levels of force development induced by carbachol were 139.1% ± 5.0% in EDNRB(-/-) rat, whereas the peak levels were 242.1% ± 27.7% in EDNRB(+/+) rat. The changes in the [Ca2+]i elevation induced by carbachol were 101.7% ± 12.2% in the homozygous rat, whereas these were 143.8% ± 8.9% in the wild-type rat. Both results in the homozygous rat significantly decreased in comparison with those of the wild rat (P < .05). The expression of the L-VOC channel mRNA also decreased in the homozygous rat. Conclusions: This is the first report to show the [Ca2+]i mobilization in the smooth muscles of the rat model of HD. The decrease in both [Ca2+]i and force development was thus considered to be due to the decrease in the Ca2+ channel expression.

ジャーナルJournal of Pediatric Surgery
出版ステータス出版済み - 10月 2007

!!!All Science Journal Classification (ASJC) codes

  • 外科
  • 小児科学、周産期医学および子どもの健康


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