Control of Motility in the Internal Anal Sphincter

The internal anal sphincter (IAS) plays an important role in the maintenance of fecal continence since it generates tone and is responsible for > 70% of resting anal pressure. During normal defecation the IAS relaxes. Historically, tone generation in gastrointestinal muscles was attributed to mechanisms arising directly from smooth muscle cells, ie, myogenic activity. However, slow waves are now known to play a fundamental role in regulating gastrointestinal motility and these electrical events are generated by the interstitial cells of Cajal. Recently, interstitial cells of Cajal, as well as slow waves, have also been identified in the IAS making them viable candidates for tone generation. In this review we discuss four different mechanisms that likely contribute to tone generation in the IAS. Three of these involve membrane potential, L-type Ca²⁺ channels and electromechanical coupling (ie, summation of asynchronous phasic activity, partial tetanus, and window current), whereas the fourth involves the regulation of myofilament Ca²⁺ sensitivity. Contractile activity in the IAS is also modulated by sympathetic motor neurons that significantly increase tone and anal pressure, as well as inhibitory motor neurons (particularly nitrergic and vasoactive intestinal peptidergic) that abolish contraction and assist with normal defecation. Alterations in IAS motility are associated with disorders such as fecal incontinence and anal fissures that significantly decrease the quality of life. Understanding in greater detail how tone is regulated in the IAS is important for developing more effective treatment strategies for these debilitating defecation disorders.

The Significance of Interstitial Cells in Neurogastroenterology

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 (PDGFRalpha+) cells generate pacemaker activity throughout the gastrointestinal (GI) tract and also transduce enteric motor nerve signals and mechanosensitivity to adjacent SMCs. ICC and PDGFRalpha+ 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.

Electrogastrography: Methodology, Validation and Applications

Electrogastrography (EGG) is a non-invasive method for the measurement of gastric myoelectrical activity. It was first discovered in 1921 and popularized in 1990s. EGG is attractive because it is non-invasive. However, due to its non-invasive nature, there have also been controversies regarding validity and applications of EGG. The aim of this review is to discuss the methodologies, validation and applications of EGG. Pros and cons of EGG will also be discussed in detail. First, the gastric slow wave and its correlation with gastric motility are presented. The association between gastric dysrhythmia and impaired gastric motility is reviewed. Secondly the method for recording the electrogastrogram is presented in detail and pitfalls in the recording and analysis of EGG are discussed. Thirdly, findings reported in the literature demonstrating the accuracy of EGG in recording gastric slow waves and gastric dysrhythmia are reviewed and discussed. The correlation of the electrogastrogram with gastric contraction is carefully discussed. Finally, applications of EGG in a few major areas are reviewed.

Hemispheric assymetry of abnormal focal EEG findings / Assimetria hemisférica de anormalidades eletrencefalográficas focais

Left and right cerebral hemispheres are morphologically similar, although they are functionally different. Focal EEG abnormalities should appear with an equal frequency in both of them, but the literature has reported a left predominance. We presented the first Latin American study on lateralization of focal EEG abnormalities. METHOD: We retrospectively studied 10,408 EEGs from April 2001 to April 2010. They were separated by age and gender to estimate the frequency of left-sided versus right-sided focal abnormalities (discharges or slow waves). Associated clinical features were also accessed. RESULTS: Discharges were more prevalent in left cerebral hemisphere, in temporal lobe, and a stronger lateralization was found among adults. Right-sided discharges occurred more in frontal lobe. Slow waves were also more prevalent in the left cerebral hemisphere and among adults. Among left-sided slow waves group, women were more prevalent. Contrarily, men were more observed among right-sided slow waves EEGs. Left-sided slow waves were more prevalent in temporal and parietal lobes. Contrarily, right-sided slow waves occurred more in frontal and occipital lobes. Epilepsy was the most frequent disease among the patients with focal discharges in both cerebral hemispheres. Right-sided slow waves were more associated to epilepsy, and left-sided slow waves were more associated to headache. CONCLUSION: There were significant differences between cerebral hemispheres on focal EEG abnormalities, considering lateralization, gender, age and clinical features. These results suggest a neurofuncional asymmetry between cerebral hemispheres which may be explained by different specificities, as well as by cerebral neuroplasticity.

Embora sejam morfologicamente semelhantes, os hemisférios cerebrais apresentam diferenças funcionais geneticamente determinadas. Ainda assim, anormalidades eletrencefalográficas focais deveriam ocorrer simetricamente numa população geral, embora a literatura tenha referido um predomínio à esquerda. Nosso objetivo é relatar o primeiro estudo latino-americano sobre uma grande série de EEGs, no intuito de observar se há lateralização de anormalidades focais. MÉTODO: Foram estudados retrospectivamente 10.408 EEGs, realizados de abril de 2001 a abril de 2010, os quais foram classificados de acordo com a presença de anormalidades focais específicas (descargas) e inespecíficas (ondas lentas focais). Os EEGs foram divididos de acordo com o gênero e a idade, e foram analisados achados clínicos associados. RESULTADOS: As descargas foram mais prevalentes no hemisfério cerebral esquerdo, no lobo temporal, observando-se uma lateralização mais forte entre os adultos. À direita, elas prevaleceram no lobo frontal. Ondas lentas focais prevaleceram também à esquerda e no lobo temporal, especialmente entre os adultos. Entre os que apresentaram ondas lentas à esquerda, observou-se maior prevalência entre as mulheres. Os homens prevaleceram entre os que apresentaram ondas lentas à direita. À esquerda, ondas lentas prevaleceram nos lobos temporal e parietal. À direita, nos lobos frontal e occipital. Epilepsia foi o achado clínico mais associado à presença de descargas em ambos os hemisférios cerebrais. Ondas lentas à direita foram mais associadas a epilepsia, enquanto que, à esquerda, elas foram mais associadas a cefaleia. CONCLUSÃO: Houve diferenças entre os hemisférios cerebrais quanto à lateralização das anormalidades focais, assim como entre os gêneros, faixas etárias analisadas e quadro clínico associado.

Detection and evaluation of gastric motility for the patients with erosive gastritis / 中国实用内科杂志

Objective In order to investigate the comlex course of electricity and mechanism of erosive gastritis(EG) and its relative factors,and to extract gastric motility feature indexes.Methods 30 volunteers of erosive gastritis were selected.The signal processing device was designed by Chongqing University of Posts and Telecommunications.By the means of spectrum analysis technic,the signals could be classified according to the dominant power and dominant frequency.Some indexes such as frequency of EGG and IGM,signal power spectrum and dynamic spectrum,the rates of rhythm and power for the normal EGG and IGM and so on could also be calculated.Results The power ratio in 2~4 cpm was 59.2?4.4,the frequency ratio was 70.4?25.5,the frequency instability coefficient was 0.182?0.059,and the power instability coefficient was 1.576?0.481.The parameters changed signifcantly between health adult and patient(P0.05).Conclusion The results of the experiments show that the method based on the synchronous measurement of EGG and IGM can provide a non-invasive way to investigate and evaluate erosive gastritis corresponding to gastrointestinal physiology and pathology conditions.

Neurotensin enhances gastric motility in antral circular muscle strip of guinea-pig

Many reports suggest that neurotensin (NT) in the gastrointestinal tract may play a possible role as a neurotransmitter, a circulating hormone, or a modulator of motor activity. NT exerts various actions in the intestine; it produces contractile and relaxant responses in intestinal smooth muscle. This study was designed to investigate the effect of NT on motility of antral circular muscle strips in guinea-pig stomach. To assess the role of Ca2+ influx in underlying mechanism, slow waves were simultaneously recorded with spontaneous contractions using conventional intracellular mircoelectrode technique. At the concentration of 10-7 M, where NT showed maximum response, NT enhanced the magnitude (863 +/- 198%, mean +/- SEM, n = 13) and the frequency (154 +/- 10.3%, n = 11) of spontaneous contractions. NT evoked a slight hyperpolarization of membrane potential, tall and steep slow waves with abortive spikes (278 +/- 50%, n = 4). These effects were not affected by atropine (2 micrometer), guanethidine (2 micrometer) and tetrodotoxin (0.2 micrometer). NT-induced contractile responses were abolished in Ca2+-free solution and reduced greatly to near abolition by 10 micrometer of verapamil or 0.2 mM of CdCl2. Verapamil attenuated the effects of NT on frequency and amplitude of the slow waves. Taken together, these results indicate that NT enhances contractility in guinea-pig gastric antral circular muscle and Ca2+ influx through the voltage-operated Ca2+ channel appears to play an important role in the NT-induced contractile mechanism.

Effects of prostaglandin E2 on the spontaneous contractions and electrical activities of the antral circular muscle in guinea-pig stomach

The spontaneous contractions of gastric smooth muscles are regulated by slow waves, which are modulated by both nervous system and humoral agents. This study was designed to examine the effects of Prostaglandin E2 (PGE2) on the contractile and electrical activities of antral smooth muscles in guinea-pig stomach, using an intracellular recording technique. To elucidate the underlying mechanism for its effect on contractility, ionic currents were also measured using a whole-cell patch clamp method. The basal tone by PGE2 was variable, whereas the magnitude of phasic contractions was reduced (19.0 +/- 2.1%, n=19). The resting membrane potentials were hyperpolarized (-4.4+/-0.5 mV, n=10), and plateau potentials were lowered (-2.9+/-0.5 mV, n=10). In most cases, however, the initial peak potentials of slow waves were depolarized more by PGE2 than those of control. The frequency of the slows wave was increased from 5.7+/-0.2 cycles/min to 6.5+/-0.2 (n-22). Voltage-operated Ca2+ currents were decreased by PGE2 (n=5). Voltage-operated K+ currents, both Ca-dependent and Ca-independent, were increased (n-5). These results suggest that PGE2 plays an important role in the modulation of gastric smooth muscle activities, and its inhibitory effects on the contractility and activities of slow waves are resulted from both decrease of Ca2+ currents and increase of K+ currents.