5 research outputs found

    Functional and molecular expression of a voltage-dependent K+ channel (Kv1.1) in interstitial cells of Cajal

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    Located within the gastrointestinal (GI) musculature are networks of cells known as interstitial cells of Cajal (ICC). ICC are associated with several functions including pacemaker activity that generates electrical slow waves and neurotransmission regulating GI motility. In this study we identified a voltage-dependent K+ channel (Kv1.1) expressed in ICC and neurons but not in smooth muscle cells.Transcriptional analyses demonstrated that Kv1.1 was expressed in whole tissue but not in isolated smooth muscle cells. Immunohistochemical co-localization of Kv1.1 with c-kit (a specific marker for ICC) and vimentin (a specific marker of neurons and ICC) indicated that Kv1.1-like immunoreactivity (Kv1.1-LI) was present in ICC and neurons of GI tissues of the dog, guinea-pig and mouse. Kv1.1-LI was not observed in smooth muscle cells of the circular and longitudinal muscle layers.Kv1.1 was cloned from a canine colonic cDNA library and expressed in Xenopus oocytes. Pharmacological investigation of the electrophysiological properties of Kv1.1 demonstrated that the mamba snake toxin dendrotoxin-K (DTX-K) blocked the Kv1.1 outward current when expressed as a homotetrameric complex (EC50 = 0.34 nm). Other Kv channels were insensitive to DTX-K. When Kv1.1 was expressed as a heterotetrameric complex with Kv1.5, block by DTX-K dominated, indicating that one or more subunits of Kv1.1 rendered the heterotetrameric channel sensitive to DTX-K.In patch-clamp experiments on cultured murine fundus ICC, DTX-K blocked a component of the delayed rectifier outward current. The remaining, DTX-insensitive current (i.e. current in the presence of 10−8m DTX-K) was outwardly rectifying, rapidly activating, non-inactivating during 500 ms step depolarizations, and could be blocked by both tetraethylammonium (TEA) and 4-aminopyridine (4-AP).In conclusion, Kv1.1 is expressed by ICC of several species. DTX-K is a specific blocker of Kv1.1 and heterotetrameric channels containing Kv1.1. This information is useful as a means of identifying ICC and in studies of the role of delayed rectifier K+ currents in ICC functions

    “Equal rites before the law”: religious celebrations of same-sex relationships in the Netherlands, 1960s–1990s

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    The opening-up of marriage to same-sex couples, which became Dutch law in 2000–2001, is often presented as a triumph of emancipation and secularization. Well into the 1990s, however, the majority of Dutch LGB organizations would have none of it – whereas Catholic and mainline Protestant initiatives at solemnizing homosexual relationships had been taken already since the 1960s. After explaining progressive, secular objections to marriage, this article discusses a number of more or less official, clerical initiatives at public, ritual recognition of same-sex relationships from the 1970s and 1980s. Next, as a historical backdrop, it sketches the emergence of a pastoral discourse on “the homophile neighbor” since the late 1950s. Lastly, it discusses three highly publicized “stunts” from 1967 to 1970. It is argued that religious institutions and traditions have not only posed an obstacle to non-heterosexuals, but offered them a repertoire of symbolic expression and contestation
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