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CRF-induced calcium signaling in guinea pig small intestine myenteric neurons involves CRF-1 receptors and activation of voltage-sensitive calcium channels.
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Simultaneous whole-cell patch-clamp and calcium imaging on myenteric neurons
No full textLive calcium imaging is often used as a proxy for electrophysiological measurements and has been a valuable tool that allows simultaneous analysis of neuronal activity in multiple cells at the population level. In the enteric nervous system, there are two main electrophysiological classes of neurons, AH- and S-neurons, which have been shown to have different calcium handling mechanisms. However, they are rarely considered separately in calcium imaging experiments. A handful of studies have shown that in guinea pig, a calcium transient will accompany a single action potential in AH-neurons, but multiple action potentials are required to generate a calcium transient in S-neurons. How this translates to different modes of cellular depolarisation and whether this is consistent across species is unknown. In this study, we used simultaneous whole-cell patch-clamp electrophysiology together with calcium imaging to investigate how enteric neurons respond to different modes of depolarisation. Using both traditional (4Hz) and also high-speed (1000Hz) imaging techniques, we found that single action potentials elicit calcium transients in both AH-neurons and S-neurons. Sub-threshold membrane depolarisations were also able to elicit calcium transients, although calcium responses were generally amplified if an action potential was present. Further, we identified that responses to nicotinic acetylcholine receptor stimulation can be used to distinguish between AH- and S-neurons in calcium imaging.</p
Histamine 1 receptor antagonisme als nieuwe behandeling voor PDS
No full textIrritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder characterized by abdominal discomfort and pain associated with altered defecation in the absence of an organic cause. Aberrant abdominal pain perception or visceral hypersensitivity is the most disturbing and therapy resistant symptom in IBS, but the underlying pathophysiological mechanisms remain largely unknown.
Mast cell activation is proposed to be involved in abnormal abdominal pain perception in IBS. Somatic pain studies indicate sensitization of nociceptors (TRPV1, TRPV4 and TRPA1) is a major mechanism by which inflammatory mediators induce increased pain perception. In the same line, we here hypothesize that mast cell mediators (histamine, serotonin, tryptase) not only directly activate visceral efferents, but also sensitize nociceptors leading to abnormal pain perception or visceral hypersensitivity. In the present project therefore, I will assess the role of mast cell mediators on sensitization of the nociceptors TRV1, TRPV4 and TRPA1 in human submucosal neurons of rectal biopsies, murine nociceptive neurons of dorsal root ganglia and murine afferent nerves. In addition, the molecular mechanisms underlying TRP sensitization will be investigated.
The results of this project will be of crucial importance to improve our insight in IBS and will lead to a more efficient treatment strategy for visceral pain.status: Publishe
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