Referenced in: none

Automatically associated channels: Cav2.2 , Slo1

Title: Spermine biphasically affects N-type calcium channel currents in adult dorsal root ganglion neurons of the rat.

Authors: Ilaria Cino, Alessandro Formenti

Journal, date & volume: Biochim. Biophys. Acta, 2008 Oct , 1778, 2437-43

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/18675782

Abstract
Spermine (Spe) is a polyamine co-secreted with neurotransmitters. In this work its effects on N-type Ca2+ channel (CaV2.2) 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 microM decreased N-type Ca2+ 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 Ca2+ currents were strongly dependent on [Ca2+]ext, high [Ca2+] 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.