Spermine (Spe) is a polyamine co-secreted with neurotransmitters. In this work its effects on N-type Ca(2+) channel (Ca(V)2.2) have been studied on adult sensory neurons of the rat by means of whole-cell patch-clamp. Spe exerted biphasic effects when added to the external solution: at 500 muM decreased N-type Ca(2+) channel currents, reducing the maximum whole-cell conductance, shifting the activation curve to the right on the voltage axes and decreasing its slope; conversely, at lower concentration (500 nM) Spe induced completely opposite effects. In 62% of the neurons the inhibitory effects were accompanied by a slowing down of the activation kinetics relieved by a conditioning pre-pulse to +50 mV. The biphasic effects and their rapid onset and offset time course may be explained if multiple sites of action with a different affinity for Spe are present directly on the channel. The effects of Spe on HVA Ca(2+) currents were strongly dependent on [Ca(2+)](ext), high [Ca(2+)] powerfully reducing Spe effects. This may be explained if we take into account that as Spe has four positive charges at physiological pH; it may compete with divalent cations for some negatively charged regulatory sites. In these experiments, Spe was effective at concentrations possibly reached in physiological conditions.
Spermine biphasically affects N-type calcium channel currents in adult dorsal root ganglion neurons of the rat / I. Cino, A. Formenti. - In: BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES. - ISSN 0005-2736. - 1778:10(2008 Oct), pp. 2437-2443.
Spermine biphasically affects N-type calcium channel currents in adult dorsal root ganglion neurons of the rat
A. FormentiUltimo
2008
Abstract
Spermine (Spe) is a polyamine co-secreted with neurotransmitters. In this work its effects on N-type Ca(2+) channel (Ca(V)2.2) have been studied on adult sensory neurons of the rat by means of whole-cell patch-clamp. Spe exerted biphasic effects when added to the external solution: at 500 muM decreased N-type Ca(2+) channel currents, reducing the maximum whole-cell conductance, shifting the activation curve to the right on the voltage axes and decreasing its slope; conversely, at lower concentration (500 nM) Spe induced completely opposite effects. In 62% of the neurons the inhibitory effects were accompanied by a slowing down of the activation kinetics relieved by a conditioning pre-pulse to +50 mV. The biphasic effects and their rapid onset and offset time course may be explained if multiple sites of action with a different affinity for Spe are present directly on the channel. The effects of Spe on HVA Ca(2+) currents were strongly dependent on [Ca(2+)](ext), high [Ca(2+)] powerfully reducing Spe effects. This may be explained if we take into account that as Spe has four positive charges at physiological pH; it may compete with divalent cations for some negatively charged regulatory sites. In these experiments, Spe was effective at concentrations possibly reached in physiological conditions.Pubblicazioni consigliate
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