Similarities of SP-, NKA- and NKB-induced currents in rat dorsal root ganglion neurons

Tachykinin (TK; including substance P (SP), neurokinin A (NKA) and neurokinin B (NKB))-induced currents (I_TKs) were studied in freshly isolated rat dorsal root ganglion (DRG) neurons using whole-cell patch clamp recording and repatch techniques. All the three I_TKs manifested features of fast activating kinetics, such as short latency and fast τ _on and τ_off, and very slow desensitization. The concentration-response relationships for TKs show: (1) compared with the concentration-response curve for NKA, the curve for NKB shifted upwards, while that for SP shifted downwards; (2) the EC₅₀ values for NKB-, NKA- and SP-activated currents were very close to each other. The I-V curves for the three TKs were basically linear and arrayed in the order of NKB>NKA>SP; the reversal potentials for the three I_TKs were all around +15 mV. Replacement of NaCl in the external solution by equimolar N-methyl-D-glucamine (NMDG) attenuated both NKA- and NKB-activated currents markedly, as it was the case with SP-activated current caused by the opening of Na⁺ preferring non-selective cation channels observed in our previous work. All the three TKs proved to inhibit coexistent GABA_A receptor-mediated current (I_GABA); this effect was removed by intracellular dialysis of GDP-β-S or H-7. However, these drugs did not block the SP-, NKA- and NKB-activated currents at all, which indicated that I_TKs were G-protein independent. In short, the responses of rat DRG neurons to SP, NKA and NKB were similar in essence, although the amplitudes of currents induced by the same concentration of the three TKs were different. Taking the results of this study and our previous studies together, we hypothesized that SP, NKA and NKB may induce inward currents through undiscovered channels that are associated with tachykinins receptors (NK1R, NK2R, NK3R, which have already been cloned), but independent of G-protein coupling and remains to be further investigated.