Do gap junctions play a role in nerve transmissions as well as pacing in mouse intestine?

Daniel, E. E.; El-Yazbi, Ahmed F.; Mannarino, Marco; Galante, Gary; Boddy, Geoffrey; Livergant, Jonathan; Eteraf-Oskouei, Tahereh

doi:10.1152/ajpgi.00428.2006

Cited by 24 publications

(22 citation statements)

References 68 publications

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“…The question whether or not ICC are involved in neurotransmission has also been investigated by using the hypothesis that neural activation by field stimulation would release neurotransmitters onto ICC and this information would be transmitted to smooth muscle cells via gap junctions. Experimental evidence showed that blockade of gap junctions did not alter neurotransmission (3,14). This is consistent with our view that neurotransmitters are secreted from nerve varicosities directly to smooth muscle cells.…”

supporting

confidence: 91%

Deficiency of intramuscular ICC increases fundic muscle excitability but does not impede nitrergic innervation

Huizinga

Liu²,

Fitzpatrick³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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The motility of the gastrointestinal tract is generated by smooth muscle cells and is controlled to a large extent by an intrinsic neural network. A gap of ∼200 nm usually separates nerve varicosities from smooth muscle cells, which suggests that direct innervation of the smooth muscle by synapses does not occur. Enteric nerves do make synapse-like contact with proposed regulatory cells, the interstitial cells of Cajal (ICC), which in turn may be in gap junction contact with smooth muscle cells. The role played by ICC in enteric innervation is controversial. Experimental evidence has been presented in vitro for the hypothesis that nitrergic inhibitory innervation is strongly reduced in the absence of ICC. However, in vivo data appear to dispute that. The present report provides evidence that explains the discrepancy between in vivo and in vitro data and provides evidence that inhibitory neurotransmitters can reach smooth muscle cells without hindrance when ICC are absent. The fundic musculature shows increased responses to substance P-mediated innervation and shows marked spontaneous activity, which is consistent with increased muscle excitability.

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supporting

confidence: 91%

Deficiency of intramuscular ICC increases fundic muscle excitability but does not impede nitrergic innervation

Huizinga

Liu²,

Fitzpatrick³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…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). Other studies have demonstrated poor coupling between the gastric ICC-MY and the adjacent circular smooth muscle cells (37,41).…”

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

confidence: 99%

“…Further investigations are needed to determine how the slow waves generated independently in the ICC-MY and in circular smooth muscle cells interact to influence the regulation of RPCs in the gut. It is noteworthy that the tight coupling between the ICC and smooth muscle cells, which is an important basis of the pacemaker hypothesis, has been questioned (37,40,43).…”

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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“…[251][252][253] The gap junction uncouplers, octanol and carbenoxolone, failed to disrupt pacemaker activity in various species, 99,254 however no tests to measure the degree of electrical uncoupling have accompanied these studies. More recently, Daniel et al 255 used peptide analogs of epitopes in the extracellular domain of connexins because these are considered to be specific gap junction uncouplers. Application of these peptide analogs had no effect on paced contractions and nerve transmissions in murine small intestine, but again no tests of electrical coupling were included in the results.…”

Section: Gap Junctions Between Interstitial Cells Of Cajal and Smoothmentioning

confidence: 99%

The Significance of Interstitial Cells in Neurogastroenterology

Blair¹,

Rhee²,

Sanders³

et al. 2014

J Neurogastroenterol Motil

112

111

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Smooth muscle layers of the gastrointestinal tract consist of a heterogeneous population of cells that include enteric neurons, several classes of interstitial cells of mesenchymal origin, a variety of immune cells and smooth muscle cells (SMCs). Over the last number of years the complexity of the interactions between these cell types has begun to emerge. For example, interstitial cells, consisting of both interstitial cells of Cajal (ICC) and platelet-derived growth factor receptor alpha-positive (PDGFRα + ) cells generate pacemaker activity throughout the gastrointestinal (GI) tract and also transduce enteric motor nerve signals and mechanosensitivity to adjacent SMCs. ICC and PDGFRα + cells are electrically coupled to SMCs possibly via gap junctions forming a multicellular functional syncytium termed the SIP syncytium. Cells that make up the SIP syncytium are highly specialized containing unique receptors, ion channels and intracellular signaling pathways that regulate the excitability of GI muscles. The unique role of these cells in coordinating GI motility is evident by the altered motility patterns in animal models where interstitial cell networks are disrupted. Although considerable advances have been made in recent years on our understanding of the roles of these cells within the SIP syncytium, the full physiological functions of these cells and the consequences of their disruption in GI muscles have not been clearly defined. This review gives a synopsis of the history of interstitial cell discovery and highlights recent advances in structural, molecular expression and functional roles of these cells in the GI tract.

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Do gap junctions play a role in nerve transmissions as well as pacing in mouse intestine?

Cited by 24 publications

References 68 publications

Deficiency of intramuscular ICC increases fundic muscle excitability but does not impede nitrergic innervation

Deficiency of intramuscular ICC increases fundic muscle excitability but does not impede nitrergic innervation

Are interstitial cells of Cajal plurifunction cells in the gut?

The Significance of Interstitial Cells in Neurogastroenterology

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