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Ascending excitatory neural pathways modulate slow phasic myogenic contractions in the isolated human colon
Author(s) -
Carbone S. E.,
Dinning P. G.,
Costa M.,
Spencer N. J.,
Brookes S. J. H.,
Wattchow D. A.
Publication year - 2013
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.12129
Subject(s) - hexamethonium , tetrodotoxin , excitatory postsynaptic potential , stimulation , medicine , endocrinology , agonist , chemistry , reflex , enteric nervous system , muscle contraction , biology , anatomy , inhibitory postsynaptic potential , receptor
Background In animal models, enteric reflex pathways have potent effects on motor activity; their roles have been much less extensively studied in human gut. The aim of this study was to determine if ascending excitatory interneuronal pathways can modulate spontaneous phasic contractions in isolated preparations of human colonic circular muscle. Methods Human colonic preparations were cut into T shapes, with vertical bar of the ‘T’ pharmacologically isolated. Electrical stimulation and the nicotinic agonist, 1,1‐dimethyl‐4‐phenylpiperazinium iodide ( DMPP ), were applied to the isolated region and circular muscle contractile activity was measured from the cross‐bar of the T, more than 10 mm orally from the region of stimulation. Key Results The predominant form of spontaneous muscle activity consisted of tetrodotoxin‐resistant, large amplitude, slow phasic contractions ( SPC s), occurring at average intervals of 124 ± 68 s. Addition of a high concentration of hexamethonium (1 mmol L −1 ) to the superfusing solution significantly increased the interval between SPC s to 278.1 ± 138.3 s ( P < 0.005). Focal electrical stimulation more than 10 mm aboral to the muscle recording site advanced the onset of the next SPC , and this effect persisted in hexamethonium. However, the effect of electrical stimulation was blocked by tetrodotoxin ( TTX , 1 μ mol L −1 ). Application of the nicotinic agonist DMPP (1 mmol L −1 ) to the aboral chamber often stimulated a premature SPC (n = 4). Conclusions & Inferences The major form of spontaneous contractility in preparations of human colonic circular muscle is SPC s, which are myogenic in origin. Activation of ascending excitatory neural pathways, which involve nicotinic receptors, can modulate the timing of SPC s and thus influence human colonic motility.