Regional differences in nitrergic innervation of the smooth muscle of murine lower oesophageal sphincter

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Abstract
Background and purpose: Anatomical and pharmacological studies have demonstrated that the lower oesophageal sphincter (LES) is not a simple homogenous circular muscle with uniform innervation. Regional differences have been demonstrated in several species including humans. We investigated, for the first time in mice LES, regionally distinct physiological and pharmacological characteristics of the neuromusculature.Experimental approach: Conventional intracellular recordings and pharmacological techniques were employed to evaluate electrical properties and functional innervation of smooth muscle cells. Results from CD1 (control), nNOS(−/−) and eNOS(−/−) genetic knockout mice were compared.Key results: Smooth muscle of sling and clasp LES displayed unitary membrane potentials of 1– 4 mV. Transmural nerve stimulation produced a monophasic inhibitory junction potential (IJP) in the sling, whereas in the clasp a biphasic IJP, consisting of a brief IJP followed by a long‐lasting slow IJP (lsIJP), was induced. Pharmacological interventions and genetically modified mice were used to demonstrate a monophasic apamin‐sensitive (purinergic) component in both LES regions. However, the nitrergic IJP was monophasic in the sling and biphasic in the clasp. Unitary membrane potentials and IJPs were not different in CD1 and eNOS(−/−) mice, suggesting no involvement of myogenic NOS.Conclusion and implications: These data in mouse LES indicate that there are previously unreported regional differences in the IJP and that both the apamin‐resistant monophasic and biphasic IJPs are mediated primarily by nitrergic innervation.British Journal of Pharmacology (2008) 153, 517–527; doi:10.1038/sj.bjp.0707573; published online 26 November 2007

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