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(TK)s) were studied in freshly isolated rat dorsal root ganglion (DRG) neurons using whole-cell patch clamp recording and repatch techniques. All the three I(TK)s manifested features of fast activating kinetics, such as short latency and fast tau(on) and tau(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 EC(50) 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(TK)s 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-beta-S or H-7. However, these drugs did not block the SP-, NKA- and NKB-activated currents at all, which indicated that I(TK)s 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.
Yang
Yun-Lei
YL
Department of Molecular and Cellular Neurobiology, Tongji Medical College of Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, PR China.
Yao
Kai-Hui
KH
Li
Zhi-Wang
ZW
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects*; D015288:Neurokinin A / Q000494:pharmacology*; D015287:Neurokinin B / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000502:physiology; D013373:Substance P / Q000494:pharmacology*; D015320:Tachykinins / Q000494:pharmacology
D018079:Receptors, GABA; D015320:Tachykinins; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B