5-HT3 Receptors in Rat Dorsal Root Ganglion Neurons: Ca(2+) Entry and Modulation of Neurotransmitter Release

Rat dorsal root ganglion (DRG) neurons express 5-hydroxytryptamine receptors (5-HT3Rs). To elucidate their physiological role in the modulation of sensory signaling, we aimed to quantify their functional expression in newborn and adult rat DRG neurons, as well as their ability to modulate the Ca(2+)-dependent neurotransmitter release, by means of electrophysiological techniques combined with fluorescence-based Ca(2+) imaging. The selective 5-HT3R agonist mCPBG (10 μM) elicited whole-cell currents in 92.5% of adult DRG neurons with a significantly higher density current than in responding newborn cells (52.2%), suggesting an increasing serotoninergic modulation on primary afferent cells during development. Briefly, 5-HT3Rs expressed by adult DRG neurons are permeable to Ca(2+) ions, with a measured fractional Ca(2+) current (i.e., the percentage of total current carried by Ca(2+) ions, Pf) of 1.0%, similar to the value measured for the human heteromeric 5-HT3(A/B) receptor (P(f) = 1.1%), but lower than that of the human homomeric 5-HT3(A) receptor (P(f) = 3.5%). mCPBG applied to co-cultures of newborn DRG and spinal neurons significantly increased the miniature excitatory postsynaptic currents (mEPSCs) frequency in a subset of recorded spinal neurons, even in the presence of Cd(2+), a voltage-activated Ca(2+) channel blocker. Considered together, our findings indicate that the Ca(2+) influx through heteromeric 5-HT3Rs is sufficient to increase the spontaneous neurotransmitter release from DRG to spinal neurons.