Spermine biphasically affects N-type calcium channel currents in adult dorsal root ganglion neurons of the rat.
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.
Cino
Ilaria
I
Institute of Human Physiology II, University of Milan, Via Mangiagalli, 32, Milan, I-20133, Italy.
Formenti
Alessandro
A
D000818:Animals; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology* / Q000187:drug effects; D015640:Ion Channel Gating; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D013096:Spermine / Q000494:pharmacology*
D020864:Calcium Channels, N-Type; D013096:Spermine