RESUMO
Heart failure is one of the most prevalent causes of death in the western world. Sea anemone contains a myriad of short peptide neurotoxins affecting many pharmacological targets, several of which possess cardiotonic activity. In the present study we describe the isolation and characterization of AdE-1 (ion channel modifier), a novel cardiotonic peptide from the sea anemone Aiptasia diaphana, which differs from other cnidarian toxins. Although AdE-1 has the same cysteine residue arrangement as sea anemone type 1 and 2 Na(+) channel toxins, its sequence contains many substitutions in conserved and essential sites and its overall homology to other toxins identified to date is low (<36%). Physiologically, AdE-1 increases the amplitude of cardiomyocyte contraction and slows the late phase of the twitch relaxation velocity with no induction of spontaneous twitching. It increases action potential duration of cardiomyocytes with no effect on its threshold and on the cell's resting potential. Similar to other sea anemone Na(+) channel toxins such as Av2 (Anemonia viridis toxin II), AdE-1 markedly inhibits Na(+) current inactivation with no significant effect on current activation, suggesting a similar mechanism of action. However, its effects on twitch relaxation velocity, action potential amplitude and on the time to peak suggest that this novel toxin affects cardiomyocyte function via a more complex mechanism. Additionally, Av2's characteristic delayed and early after-depolarizations were not observed. Despite its structural differences, AdE-1 physiologic effectiveness is comparable with Av2 with a similar ED(50) value to blowfly larvae. This finding raises questions regarding the extent of the universality of structure-function in sea anemone Na(+) channel toxins.
Assuntos
Venenos de Cnidários , Potenciais da Membrana/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Peptídeos , Anêmonas-do-Mar , Bloqueadores dos Canais de Sódio , Animais , Células Cultivadas , Venenos de Cnidários/química , Venenos de Cnidários/genética , Venenos de Cnidários/metabolismo , Venenos de Cnidários/farmacologia , Masculino , Miócitos Cardíacos/patologia , Peptídeos/química , Peptídeos/genética , Peptídeos/metabolismo , Peptídeos/farmacologia , Ratos , Ratos Sprague-Dawley , Anêmonas-do-Mar/química , Anêmonas-do-Mar/genética , Bloqueadores dos Canais de Sódio/química , Bloqueadores dos Canais de Sódio/metabolismo , Bloqueadores dos Canais de Sódio/farmacologiaRESUMO
The understanding of how neurons interact in the visual cortex and what types of neurons are responsable for each interaction are still open questions. In order to analyse such problem, the spiking activity of neurons in the central visual pathway of awake owls was analyzed with Principal Component Analysis (PCA) and clustering techniques. Further analysis using kernel representation revealed the existence of two large groups of neurons with distinguishable behavior.