Background
Intramuscular interstitial cells of Cajal (ICC-IM) have been shown to participate in nitrergic neuromuscular transmission (NMT) in various regions of the gastrointestinal (GI) tract but their role in the internal anal sphincter (IAS) is still uncertain. Contractile studies of the IAS in the W/Wv mouse (a model in which ICC-IM numbers are markedly reduced) have reported that nitrergic NMT persists and that ICC-IM are not required. However, neither the changes in electrical events underlying NMT nor the contributions of other non-nitrergic neural pathways have been examined in this model.
Methods
The role of ICC-IM in NMT was examined by recording the contractile and electrical events associated with electrical field stimulation (EFS) of motor neurons in the IAS of wildtype and W/Wv mice. Nitrergic, purinergic and cholinergic components were identified using inhibitors of these pathways.
Key Results
Under NANC conditions, purinergic, and nitrergic pathways both contribute to EFS induced inhibitory junction potentials (IJPs) and relaxation. Purinergic IJPs and relaxation were intact in the W/Wv mouse IAS whereas nitrergic IJPs were reduced by 50–60% while relaxation persisted. In the presence of L-NNA (NOS inhibitor) and MRS2500 (P2Y1 receptor antagonist), EFS gave rise to cholinergic depolarization and contractions that were abolished by atropine. Cholinergic depolarization was absent in the W/Wv mouse IAS while contraction persisted.
Conclusions and Inferences
ICC-IM significantly contribute to the electrical events underlying nitrergic and cholinergic NMT whereas contractile events persist in the absence of ICC-IM. The purinergic inhibitory neural pathway appears to be independent of ICC-IM.
Key points• Vasoactive intestinal polypeptide (VIP)-ergic neuromuscular transmission (NMT) was examined in the internal anal sphincter of wild-type mice and compared with that of VIP −/− mice.• Relaxation and hyperpolarization during brief trains of electrical field stimulation (EFS; 4 s) were mediated by purinergic and nitrergic NMT.• During longer stimulus trains, a non-purinergic, non-nitrergic (NNNP) relaxation and hyperpolarization slowly developed and persisted for several minutes beyond the end of the stimulus train.• The NNNP NMT was abolished by VIP receptor antagonists, absent in the VIP −/− mouse internal anal sphincter and mimicked by exogenous VIP.• These data suggest that NNNP NMT gives rise to ultraslow relaxation and hyperpolarization that is mediated by VIP. In vivo, this pathway may be activated with larger rectal distensions, leading to a more prolonged anal relaxation.Abstract There is evidence that vasoactive intestinal polypeptide (VIP) participates in inhibitory neuromuscular transmission (NMT) in the internal anal sphincter (IAS). However, specific details concerning VIP-ergic NMT are limited, largely because of difficulties in selectively blocking other inhibitory neural pathways. The present study used the selective P2Y 1 receptor antagonist MRS2500 (1 μM) and the nitric oxide synthase inhibitor N G -nitro-L-arginine (L-NNA; 100 μM) to block purinergic and nitrergic NMT to characterize non-purinergic, non-nitrergic (NNNP) inhibitory NMT and the role of VIP in this response. Nerves were stimulated with electrical field stimulation (0.1-20 Hz, 4-60 s) and the associated changes in contractile and electrical activity measured in non-adrenergic, non-cholinergic conditions in the IAS of wild-type and VIP −/− mice. Electrical field stimulation gave rise to frequency-dependent relaxation and hyperpolarization that was blocked by tetrodotoxin. Responses during brief trains of stimuli (4 s) were mediated by purinergic and nitrergic NMT. During longer stimulus trains, an NNNP relaxation and hyperpolarization developed slowly and persisted for several minutes beyond the end of the stimulus train. The NNNP NMT was abolished by VIP6-28 (30 μM), absent in the VIP −/− mouse and mimicked by exogenous VIP (1-100 nM). Immunoreactivity for VIP was co-localized with neuronal nitric oxide synthase in varicose intramuscular fibres but was not detected in the VIP −/− mouse IAS. In conclusion, this study identified an ultraslow component of inhibitory NMT in
This study investigated the availability and accessibility of lifting/handling aids in hospitals, their use by hospital nurses and the training received in their use. Handling slings were the most widely available, and found on 93% of wards. Aids were underused. No aid was used for 65.8% of manual handling activities carried out on the previous working day. Training varied considerably.
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