N-type calcium channels are omega-conotoxin (omega-CgTx)-sensitive, voltage-dependent ion channels involved in the control of neurotransmitter release from neurons. Multiple subtypes of voltage-dependent calcium channel complexes exist, and it is the alpha 1 subunit of the complex that forms the pore through which calcium enters the cell. The primary structures of human neuronal calcium channel alpha 1B subunits were deduced by the characterization of overlapping complementary DNAs. Two forms (alpha 1B-1 and alpha 1B-2) were identified in human neuroblastoma (IMR32) cells and in the central nervous system, but not in skeletal muscle or aorta tissues. The alpha 1B-1 subunit directs the recombinant expression of N-type calcium channel activity when it is transiently co-expressed with human neuronal beta 2 and alpha 2b subunits in mammalian HEK293 cells. The recombinant channel was irreversibly blocked by omega-CgTx but was insensitive to dihydropyridines. The alpha 1B-1 alpha 2b beta 2-transfected cells displayed a single class of saturable, high-affinity (dissociation constant = 55 pM) omega-CgTx binding sites. Co-expression of the beta 2 subunit was necessary for N-type channel activity, whereas the alpha 2b subunit appeared to modulate the expression of the channel. The heterogeneity of alpha 1B subunits, along with the heterogeneity of alpha 2 and beta subunits, is consistent with multiple, biophysically distinct N-type calcium channels.
SUMMARYOrf virus has a worldwide distribution among sheep and goats. The hypersensitivity reaction erythema multiforme (EM) is a known complication of orf infection in humans; however, its occurrence is poorly understood and has not been extensively reviewed. We present two unrelated cases of orf-associated EM, and a review of the literature, highlighting important clinical, epidemiological and immunological aspects of this condition. Orf and its associated complications can occur in rural areas, as well as urban settings, where it is less well-known, through religious or cultural practices involving animal slaughter. Obtaining a history of animal exposures from patients with lesions suspicious for orf and secondary skin eruptions can guide diagnosis and identification of the inciting immune stimulus. Determining the pathophysiology and relative contribution of host and viral factors contributing to EM and other orf-associated hypersensitivity reactions could facilitate the identification of risk factors and inform treatment decisions.
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