Spontaneous electrical rhythmicity and the role of the sarcoplasmic reticulum in the excitability of guinea pig gallbladder smooth muscle cells

被引:20
作者
Balemba, OB
Salter, MJ
Heppner, TJ
Bonev, AD
Nelson, MT
Mawe, GM
机构
[1] Univ Vermont, Dept Anat & Neurobiol, Burlington, VT 05405 USA
[2] Univ Vermont, Dept Pharmacol, Burlington, VT 05405 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2006年 / 290卷 / 04期
关键词
calcium transients; gallbladder motility; slow waves; action potentials;
D O I
10.1152/ajpgi.00310.2005
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Spontaneous action potentials and Ca2+ transients were investigated in intact gallbladder preparations to determine how electrical events propagate and the cellular mechanisms that modulate these events. Rhythmic phasic contractions were preceded by Ca2+ flashes that were either focal ( limited to one or a few bundles), multifocal ( occurring asynchronously in several bundles), or global ( simultaneous flashes throughout the field). Ca2+ flashes and action potentials were abolished by inhibiting sarcoplasmic reticulum (SR) Ca2+ release via inositol (1,4,5)- trisphosphate [Ins(1,4,5)P-3] channels with 2-aminoethoxydiphenyl borate and xestospongin C or by inhibiting voltage-dependent Ca2+ channels (VDCCs) with nifedipine or diltiazem or nisoldipine. Inhibiting ryanodine channels with ryanodine caused multiple spikes superimposed upon plateaus of action potentials and extended quiescent periods. Depletion of SR Ca2+ stores with thapsigargin or cyclopiazonic acid increased the frequency and duration of Ca2+ flashes and action potentials. Acetylcholine, carbachol, or cholecystokinin increased synchronized and increased the frequency of Ca2+ flashes and action potentials. The phospholipase C (PLC) inhibitor U-73122 did not affect Ca2+ flash or action potential activity but inhibited the excitatory effects of acetylcholine on these events. These results indicate that Ca2+ flashes correspond to action potentials and that rhythmic excitation in the gallbladder is multifocal among gallbladder smooth muscle bundles and can be synchronized by excitatory agonists. These events do not depend on PLC activation, but agonist stimulation involves activation of PLC. Generation of these events depends on Ca2+ entry via VDCCs and on Ca2+ mobilization from the SR via Ins( 1,4,5) P3 channels.
引用
收藏
页码:G655 / G664
页数:10
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