Modulation of sodium currents in rat sensory neurons by nucleotides

Abstract

The effects of various nucleotides on the fast tetrodotoxin-sensitive (f-TTX-S) and the slow tetrodotoxin-resistant (s-TTX-R) sodium currents in rat dorsal root ganglion (DRG) neurons were investigated using the patch-clamp technique. Nucleoside triphosphates (NTPs; ATP, GTP, UTP and CTP) and nucleoside diphosphates (NDPs; ADP, GDP, UDP and CDP) decreased f-TTX-S current, whereas they increased s-TTX-R current, when currents were evoked by step depolarizations to 0 mV from a holding potential of −80 mV. NTPs and NDPs shifted both the conductance–voltage relationship curve and the steady-state inactivation curve in the hyperpolarizing direction in both types of sodium currents. Most of them also increased the maximum conductance of s-TTX-R current. ITP, a derivative of ribonucleotide, and dTTP, a deoxyribonucleotide, modulated both types of sodium currents similarly to NTPs and NDPs. However, nucleoside monophosphates (NMPs; AMP, GMP, UMP and CMP) and adenosine had little or no effect on either type of sodium current. Therefore, it seems that nucleotides, regardless of the kind of base, should have two or more phosphates to be able to modulate sodium currents in DRG neurons. Extracellular nucleotides with di- or tri-phosphates would influence the perception by modulating sodium currents in sensory neurons. Particularly, the increase of the maximum conductance and the hyperpolarizing shift of the conductance–voltage relationship of s-TTX-R sodium current would result in an intensified nociception.