Actions of ethanolamine on cultured sensory neurones from neonatal rats

Some of the analgesic and antinociceptive properties of the endocannabinoid anandamide can be explained by modulation of voltage-activated ion channels. However, the products of anandamide metabolism by fatty acid amide hydroxylase may also contribute to the altered excitability of sensory neurones. Ethanolamine is a product of metabolism of acylethanolamines including anandamide. In this study whole cell patch clamp recording and fura-2 Ca2+ imaging techniques were used to characterize its actions on neonatal rat cultured dorsal root ganglion neurones. Ethanolamine (1 μM) increased the mean Ca2+ transient produced by 1 mM caffeine and modulated Ca2+ transients evoked by 60 mM KCl. Thapsigargicin (500 nM) inhibited the ethanolamine-evoked enhancement of Ca2+ transients evoked by depolarisation. Voltage-activated K+ currents were evoked from a holding potential of −70 mV by voltage step commands to 0 mV. Acute application of 1 μM ethanolamine produced irreversible current modulation. However, application of 100 nM ethanolamine reversibly increased or decreased K+ currents. These effects of ethanolamine on voltage-activated K+ currents were not sensitive to continual application of thapsigargicin. When applied alone thapsigargicin (500 nM) had no action on the mean K+ current. In conclusion, ethanolamine may play distinct roles in the modulation of sensory neurone excitability by acting via different mechanisms to modulate K+ channels and a component of intracellular Ca2+ signalling. These data suggest that in a therapeutic context it may be difficult to predict the consequences of manipulating anandamide levels.