Identification of amino acid residues lining the pore of a gap junction channel

Gap junctions represent a ubiquitous and integral part of multicellular organisms, providing the only conduit for direct exchange of nutrients, messengers and ions between neighboring cells. However, at the molecular level we have limited knowledge of their endogenous permeants and selectivity features. By probing the accessibility of systematically substituted cysteine residues to thiol blockers (a technique called SCAM), we have identified the pore-lining residues of a gap junction channel composed of Cx32. Analysis of 45 sites in perfused Xenopus oocyte pairs defined M3 as the major pore-lining helix, with M2 (open state) or M1 (closed state) also contributing to the wider cytoplasmic opening of the channel. Additional mapping of a close association between M3 and M4 allowed the helices of the low resolution map (Unger et al., 1999. Science. 283:1176–1180) to be tentatively assigned to the connexin transmembrane domains. Contrary to previous conceptions of the gap junction channel, the residues lining the pore are largely hydrophobic. This indicates that the selective permeabilities of this unique channel class may result from novel mechanisms, including complex van der Waals interactions of permeants with the pore wall, rather than mechanisms involving fixed charges or chelation chemistry as reported for other ion channels

Neurotoxocarosis Neurotoxocaríase

Infection of humans with embryonated eggs of Toxocara canis (larva migrans) remains asymptomatic, or results in covert or common toxocarosis, visceral larva migrans syndrome, or ophthalmologic and neurologic impairment. Though neurological manifestations of Toxocara canis larvae are rare, toxocarosis remains an important differential diagnosis of various neurological disorders. Manifestations of the central nervous system are dementia, meningo-encephalitis, myelitis, cerebral vasculitis, epilepsy, or optic neuritis. Manifestations of the peripheral nervous system comprise radiculitis, affection of cranial nerves, or musculo-skeletal involvement. If toxocarosis is neglected, ignored, or refused as a differential of these abnormalities, it may be easily overlooked for years. Early recognition and treatment of the infection is, however, of paramount importance since it reduces morbidity and mortality and the risk of secondary superinfection. Like the visceral manifestations, neurological manifestations of toxocarosis are treated by benzimidazole components, most frequently albendazole, corticosteroids, or diethylcarbamazine. If detected and treated early, the prognosis of neurological manifestations of toxocarosis is favourable.<br>Infecção humana com ovos embrionados de Toxocara canis (larva migrans) pode permanecer assintomática ou resultar em toxocaríase acentuada ou comum, síndrome da larva migrans visceral ou manifestações neurológicas ou oftalmológicas. Embora manifestações neurológicas das larvas de Toxocara canis sejam raras, a toxocaríase permanece como importante diagnóstico diferencial de várias manifestações neurológicas. Manifestações do sistema nervoso central são demência, meningoencefalite, mielite, vasculite cerebral, epilepsia, ou neurite ótica. Manifestações do sistema nervoso periférico compreendem radiculite, agressão de nervos cranianos ou envolvimento músculo-esquelético. Se a toxocaríase é negligenciada, ignorada, ou recusada como diferencial destas anormalidades, ela pode ser facilmente desapercebida por anos. Reconhecimento precoce de tratamento da infecção é portanto de fundamental importância uma vez que reduz sua morbidade e mortalidade e o risco de superinfecção secundária. Da mesma maneira que as manifestações viscerais, as neurológicas são tratadas por benzimidazólicos, mais freqüentemente albendazole, corticosteróides ou dietilcarbamazine. Se detectado e tratado precocemente, o prognóstico das manifestações neurológicas da toxocaríase é favorável