ICC pacing mechanisms in intact mouse intestine differ from those in cultured or dissected intestine

Boddy, Geoffrey; Bong, Alicia; Cho, Woo-Jung; Daniel, E. E.

doi:10.1152/ajpgi.00382.2003

Cited by 28 publications

(37 citation statements)

References 42 publications

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“…These results are consistent with previous observations in GBSM cells (24,29) and other visceral smooth muscle cells (9,42). The time-dependent decreases of these events caused by prolonged exposure (not significant) are similar to the observations on slow waves in the small intestine (4,19); however, unlike in the gallbladder, SERCA pump inhibitors did not cause a transient augmentation of slow wave action potential in the small intestine (17) and inhibited slow waves and spontaneous transient depolarizations in the guinea pig gastric pylorus (36,37).…”

Section: Discussionsupporting

confidence: 93%

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

Balemba

Salter²,

Heppner³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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. Spontaneous electrical rhythmicity and the role of the sarcoplasmic reticulum in the excitability of guinea pig gallbladder smooth muscle cells. Am J Physiol Gastrointest Liver Physiol 290: G655-G664, 2006. First published November 17, 2005 doi:10.1152/ajpgi.00310.2005.-Spontaneous action potentials and Ca 2ϩ 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 Ca 2ϩ 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). Ca 2ϩ flashes and action potentials were abolished by inhibiting sarcoplasmic reticulum (SR) Ca 2ϩ 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 Ca 2ϩ 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 Ca 2ϩ stores with thapsigargin or cyclopiazonic acid increased the frequency and duration of Ca 2ϩ flashes and action potentials. Acetylcholine, carbachol, or cholecystokinin increased synchronized and increased the frequency of Ca 2ϩ flashes and action potentials. The phospholipase C (PLC) inhibitor U-73122 did not affect Ca 2ϩ flash or action potential activity but inhibited the excitatory effects of acetylcholine on these events. These results indicate that Ca 2ϩ 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 Ca 2ϩ entry via VDCCs and on Ca 2ϩ mobilization from the SR via Ins(1,4,5)P3 channels. calcium transients; gallbladder motility; slow waves; action potentials THE GALLBLADDER, which is derived from the foregut, differs from the gastrointestinal (GI) tract in the structural organization of its wall musculature (1) and motor patterns. The gallbladder muscularis propria is composed of a single layer in which gallbladder smooth muscle (GBSM) occurs in interdigitating bundles of variable sizes that either converge, diverge, or overlap and are separated by variable amounts of connective tissue. The architectural and topographical organization is nonuniform regionally; interdigitation between bundles does not present a specified pattern and some bundles extend into the submucosal layer. Unlike the gut, the gallbladder is a tonic, compliant organ that is capable of storing a large volume of bile that is released postprandially after appropriate neurohumoral stimulations (20,21). While the gallbladder functions as a tonic organ, the membranes of individual GBSM cell...

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Section: Discussionsupporting

confidence: 93%

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

Balemba

Salter²,

Heppner³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…For example, the K ϩ channels play a key role in maintaining the RMP of the gut smooth muscle cells. The alterations in calcium release by IP 3 receptors also lead to suppression or loss of slow-wave activity (16,42,99,158). The only sure way to determine that the circular smooth muscle cells do not generate spontaneous slow waves is to record from them with microelectrodes in intact W/W v or Sl/Sl mice or the Ws/Ws rats.…”

Section: The Roles Of Icc In the Generation And Propagation Of Slow Wmentioning

confidence: 99%

“…The role of the gap junctions, one of the critical components of the pacemaker hypothesis, has been questioned (12,16,40,142). The disruption of the gap junctions by pharmacological agents has little effect on the slow-wave activity in the circular muscle cells of intact muscle strips (40,43,142).…”

Section: The Roles Of Icc In the Generation And Propagation Of Slow Wmentioning

confidence: 99%

Are interstitial cells of Cajal plurifunction cells in the gut?

Sarna¹

2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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The proposed functions of the interstitial cells of Cajal (ICC) are to 1) pace the slow waves and regulate their propagation, 2) mediate enteric neuronal signals to smooth muscle cells, and 3) act as mechanosensors. In addition, impairments of ICC have been implicated in diverse motility disorders. This review critically examines the available evidence for these roles and offers alternate explanations. This review suggests the following: 1) The ICC may not pace the slow waves or help in their propagation. Instead, they may help in maintaining the gradient of resting membrane potential (RMP) through the thickness of the circular muscle layer, which stabilizes the slow waves and enhances their propagation. The impairment of ICC destabilizes the slow waves, resulting in attenuation of their amplitude and impaired propagation.2) The one-way communication between the enteric neuronal varicosities and the smooth muscle cells occurs by volume transmission, rather than by wired transmission via the ICC. 3) There are fundamental limitations for the ICC to act as mechanosensors.4) The ICC impair in numerous motility disorders. However, a cause-and-effect relationship between ICC impairment and motility dysfunction is not established. The ICC impair readily and transform to other cell types in response to alterations in their microenvironment, which have limited effects on motility function. Concurrent investigations of the alterations in slow-wave characteristics, excitationcontraction and excitation-inhibition couplings in smooth muscle cells, neurotransmitter synthesis and release in enteric neurons, and the impairment of the ICC are required to understand the etiologies of clinical motility disorders. smooth muscle; slow waves; enteric neurons; excitation-contraction coupling; peristaltic reflex; motility disorders; volume transmission; synaptic transmission, ICC THE INTERSTITIAL CELLS WERE characterized originally by Raymond V. Cajal (20,21). These cells got his attention and that of others because they are intercalated between the autonomic nerves and the effector cells. On the basis of the understanding of the interneuronal communication in the central nervous system (CNS) at that time, Cajal proposed that the intercalating cells [later called the interstitial cells of Cajal (ICC)] mediate the transmission of signals from the autonomic neurons to the smooth muscle cells. A few years later, Keith (84) observed a collar of similar cells in the myenteric plexus of the rat ileocecal junction. He was looking for a pacemaker of the gut smooth muscle electrical activity because a few years earlier he had identified such a pacemaker in the sinoatrial node of the heart. He hypothesized that those interstitial cells were the pacemaker cells in the gut. In the late 1960s and early 1970s, several investigators described a plexus of the ICC within the myenteric and submucosal plexi of the small and large intestines. They also identified close connections between the enteric axonal varicosities and ICC processes on one side and g...

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“…Among these are 1) LM pacing is faster than in the CM and is increased by TTX and L-NNA in CM, not LM; 2) robust pacing is present in the LM of w/w v mice, which lack ICC of the myenteric plexus (32); and 3) differences occur in the effects of agents such as SNP and forskolin (3,13). In the present study, electron microscopic examination of the CM layer of the Cav1 Ϫ/Ϫ mouse small intestine showed that, unlike LM, they retained some caveolar structures that were in the outer CM layer but not the inner CM layer.…”

Section: Discussionmentioning

confidence: 99%

Impact of caveolin-1 knockout on NANC relaxation in circular muscles of the mouse small intestine compared with longitudinal muscles

El-Yazbi

Cho

Boddy

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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. Impact of caveolin-1 knockout on NANC relaxation in circular muscles of the mouse small intestine compared with longitudinal muscles. Am J Physiol Gastrointest Liver Physiol 290: G394 -G403, 2006. First published September 15, 2005 doi:10.1152/ajpgi.00321.2005.-Recently, we showed that caveolin-1 (cav1) knockout mice (Cav1 Ϫ/Ϫ mice) have impaired nitric oxide (NO) function in the longitudinal muscle (LM) layer of the small intestine. The defect was a reduced responsiveness of the muscles to NO compensated by an increase in the function of apamin-sensitive, nonadrenergic, noncholinergic (NANC) mediators. In the present study, we examined similarly the effects of cav1 knockout on the relaxation in circular muscle (CM) of the mouse small intestine. CM of Cav1Ϫ/Ϫ mice also showed defective NO function, but less than in LM, as well as more activation of apamin-sensitive NANC mediators. CM of Cav1Ϫ/Ϫ mice, like LM, lacked cav1 but retained small amounts of cav3 and caveolae in the outer CM layer. In addition, we also examined the effects of a soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo-[4,3-␣]quinazolin-1-one (ODQ), on electric field stimulation (EFS)-mediated relaxation in both LM and CM. ODQ had an effect similar to the block of NO synthesis. Moreover, we compared the actions of two NO donors in the LM and CM of control and Cav1 Ϫ/Ϫ mice. Similar to LM, CM of Cav1 Ϫ/Ϫ mice showed a reduced responsiveness to the NO donors sodium nitroprusside and S-nitroso-N-acetyl penicillamine. However, both ODQ and apamin blocked the inhibitory effects of the NO donors in LM, whereas apamin had no effect in CM. In conclusion, cav1 knockout affects NO function in both LM and CM, but its effects in CM differ significantly.

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ICC pacing mechanisms in intact mouse intestine differ from those in cultured or dissected intestine

Cited by 28 publications

References 42 publications

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

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

Are interstitial cells of Cajal plurifunction cells in the gut?

Impact of caveolin-1 knockout on NANC relaxation in circular muscles of the mouse small intestine compared with longitudinal muscles

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