期刊
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
卷 84, 期 6, 页码 589-599出版社
NATL RESEARCH COUNCIL CANADA-N R C RESEARCH PRESS
DOI: 10.1139/Y06-009
关键词
interstitial cells of Cajal (ICC); gradient of pacing frequency; lidocaine; 4,4 '-diisothiocyanatostilbene-2,2 '-disulfonic acid (DIDS)
Pacing of intestinal smooth muscle is driven by a network of cells found in the myenteric plexus called the interstitial cells of Cajal (ICC-MP), which produce a rhythmic pacemaker current. Using intact segments of circular (CM) and longitudinal (LM) muscle from wild-type and W/W-V mice, we found that sodium-, chloride-, and mibefradil-sensitive ion channel currents are required for normal pacing to occur. Application of 30 mu mol/L and 300 mu mol/L lidocaine, 1 mmol/L 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), 50 nmol/L and 500 nmol/L mibefradil, or low sodium Krebs significantly reduced pacing frequency in LM and CM. However, simultaneously applying DIDS and lidocaine or low sodium Krebs solution did not completely block pacing nor did it have an additive effect. Lidocaine and low sodium Krebs solution also abolished the gradient of pacing frequencies (higher proximally) found throughout the intestine, resulting in a uniform contraction frequency of 30-40/min. In W/W-V mice, which lack ICC-MP, application of DIDS and lidocaine had no effect on the robust pacing in LM segments. In conclusion we found that sodium-, chloride-, and mibefradil-sensitive channel activities were required for normal pacing and to maintain the pacing gradient found throughout the intestines in wild-type but not W/W-V mice.
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