Spatial and temporal mapping of pacemaker activity in interstitial cells of Cajal in mouse ileum in situ

被引:83
作者
Park, KJ [1 ]
Hennig, GW [1 ]
Lee, HT [1 ]
Spencer, NJ [1 ]
Ward, SM [1 ]
Smith, TK [1 ]
Sanders, KM [1 ]
机构
[1] Univ Nevada, Sch Med, Dept Physiol & Cell Biol, Reno, NV 89557 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2006年 / 290卷 / 05期
关键词
Ca2+ signaling; slow waves; gastrointestinal motility;
D O I
10.1152/ajpcell.00447.2005
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 Ca2+ 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 Ca2+ transients that occurred after electrical slow waves. ICC-MY formed networks, and Ca2+ transient wave fronts propagated through the ICC-MY networks at similar to 2 mm/s and activated attached longitudinal muscle fibers. Nicardipine blocked Ca2+ 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 Ca2+ entry (Ni2+ 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 Ca2(+) transients in ICC-MY. These data show that global Ca2+ 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 Ca2+ handling mechanisms and entrained by voltage-dependent Ca2+ entry and coupling of cells via gap junctions.
引用
收藏
页码:C1411 / C1427
页数:17
相关论文
共 45 条
  • [21] A Ca2+-inhibited non-selective cation conductance contributes to pacemaker currents in mouse interstitial cell of Cajal
    Koh, SD
    Jun, JY
    Kim, TW
    Sanders, KM
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 2002, 540 (03): : 803 - 814
  • [22] Longitudinal and circumferential spike patches in the canine small intestine in vivo
    Lammers, WJEP
    Donck, L
    Schuurkes, JAJ
    Stephen, B
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2003, 285 (05): : G1014 - G1027
  • [23] COMPARISON OF IONIC CURRENTS FROM INTERSTITIAL-CELLS AND SMOOTH-MUSCLE CELLS OF CANINE COLON
    LEE, HK
    SANDERS, KM
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 1993, 460 : 135 - 152
  • [24] Interstitial cells of Cajal generate electrical slow waves in the murine stomach
    Ördög, T
    Ward, SM
    Sanders, KM
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 1999, 518 (01): : 257 - 269
  • [25] SIMULTANEOUS MEASUREMENT OF MEMBRANE-POTENTIAL, CYTOSOLIC CA2+, AND TENSION IN INTACT SMOOTH MUSCLES
    OZAKI, H
    STEVENS, RJ
    BLONDFIELD, DP
    PUBLICOVER, NG
    SANDERS, KM
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1991, 260 (05): : C917 - C925
  • [26] ARE RELAXATION-OSCILLATORS AN APPROPRIATE MODEL OF GASTROINTESTINAL ELECTRICAL-ACTIVITY
    PUBLICOVER, NG
    SANDERS, KM
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 256 (02): : G265 - G274
  • [27] Interstitial cells of Cajal as pacemakers in the gastrointestinal tract
    Sanders, KM
    Koh, SD
    Ward, SM
    [J]. ANNUAL REVIEW OF PHYSIOLOGY, 2006, 68 : 307 - 343
  • [28] SLOW WAVES ACTIVELY PROPAGATE AT SUBMUCOSAL SURFACE OF CIRCULAR LAYER IN CANINE COLON
    SANDERS, KM
    STEVENS, R
    BURKE, E
    WARD, SM
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1990, 259 (02): : G258 - G263
  • [29] Sanders KM, 2000, NEWS PHYSIOL SCI, V15, P291
  • [30] Spatiotemporal electrical and motility mapping of distension-induced propagating oscillations in the murine small intestine
    Seerden, TC
    Lammers, WJEP
    De Winter, BY
    De Man, JG
    Pelckmans, PA
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2005, 289 (06): : G1043 - G1051