PMID- 16381798
OWN - NLM
STAT- MEDLINE
DCOM- 20060522
LR  - 20200930
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 290
IP  - 5
DP  - 2006 May
TI  - Spatial and temporal mapping of pacemaker activity in interstitial cells of Cajal 
      in mouse ileum in situ.
PG  - C1411-27
AB  - Spontaneous electrical pacemaker activity occurs in tunica muscularis of the 
      gastrointestinal tract and drives phasic contractions. Interstitial cells of 
      Cajal (ICC) are the pacemaker cells that generate and propagate electrical slow 
      waves. We used Ca(2+) imaging to visualize spontaneous rhythmicity in ICC in the 
      myenteric region (ICC-MY) of the murine small intestine. ICC-MY, verified by 
      colabeling with Kit antibody, displayed regular Ca(2+) transients that occurred 
      after electrical slow waves. ICC-MY formed networks, and Ca(2+) transient wave 
      fronts propagated through the ICC-MY networks at approximately 2 mm/s and 
      activated attached longitudinal muscle fibers. Nicardipine blocked Ca(2+) 
      transients in LM but had no visible effect on the transients in ICC-MY. 
      beta-Glycyrrhetinic acid reduced the coherence of propagation, causing single 
      cells to pace independently. Thus, virtually all ICC-MYs are spontaneously 
      active, but normal activity is organized into propagating wave fronts. Inhibitors 
      of dihydropyridine-resistant Ca(2+) entry (Ni(2+) and mibefradil) and elevated 
      external K(+) reduced the coherence and velocity of propagation, eventually 
      blocking all activity. The mitochondrial uncouplers, FCCP, and antimycin and the 
      inositol 1,4,5-trisphosphate receptor-inhibitory drug, 2-aminoethoxydiphenyl 
      borate, abolished rhythmic Ca(2+) transients in ICC-MY. These data show that 
      global Ca(2+) transients in ICC-MYs are a reporter of electrical slow waves in 
      gastrointestinal muscles. Imaging of ICC networks provides a unique multicellular 
      view of pacemaker activity. The activity of ICC-MY is driven by intracellular 
      Ca(2+) handling mechanisms and entrained by voltage-dependent Ca(2+) entry and 
      coupling of cells via gap junctions.
FAU - Park, Kyu Joo
AU  - Park KJ
AD  - Department of Physiology and Cell Biology, University of Nevada School of 
      Medicine, Reno, NV 89557, USA.
FAU - Hennig, Grant W
AU  - Hennig GW
FAU - Lee, Hyun-Tai
AU  - Lee HT
FAU - Spencer, Nick J
AU  - Spencer NJ
FAU - Ward, Sean M
AU  - Ward SM
FAU - Smith, Terence K
AU  - Smith TK
FAU - Sanders, Kenton M
AU  - Sanders KM
LA  - eng
GR  - DK 41315/DK/NIDDK NIH HHS/United States
GR  - P20 RR 18751/RR/NCRR NIH HHS/United States
GR  - R01 DK 45713/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20051228
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
SB  - IM
MH  - Action Potentials/*physiology
MH  - Animals
MH  - Biological Clocks/*physiology
MH  - Calcium Signaling/*physiology
MH  - Cells, Cultured
MH  - Female
MH  - Ileum/cytology/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microscopy, Fluorescence/*methods
MH  - Myocytes, Smooth Muscle/*physiology
EDAT- 2005/12/31 09:00
MHDA- 2006/05/23 09:00
CRDT- 2005/12/31 09:00
PHST- 2005/12/31 09:00 [pubmed]
PHST- 2006/05/23 09:00 [medline]
PHST- 2005/12/31 09:00 [entrez]
AID - 00447.2005 [pii]
AID - 10.1152/ajpcell.00447.2005 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2006 May;290(5):C1411-27. doi: 
      10.1152/ajpcell.00447.2005. Epub 2005 Dec 28.