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.
|Titolo:||Spermine biphasically affects N-type calcium channel currents in adult dorsal root ganglion neurons of the rat|
FORMENTI, ALESSANDRO (Ultimo)
|Settore Scientifico Disciplinare:||Settore BIO/09 - Fisiologia|
|Data di pubblicazione:||ott-2008|
|Digital Object Identifier (DOI):||10.1016/j.bbamem.2008.07.006|
|Appare nelle tipologie:||01 - Articolo su periodico|