Substance P inhibits potassium and calcium currents in inner ear spiral ganglion neurons

Substance P (SP), a member of the tachykinin family of neurotransmitters and neuromodulators, has been identified on spiral ganglion neurons (SGNs) in the inner ear; however, its high affinity receptor, neurokinin-1 (NK1), has not been identified and the physiological effects of SP on SGNs are not well understood. To address these issues, immunolabeling, RT-PCR, Western blots and whole-cell patch-clamp recordings were made from SGNs in P0-P5 mouse cochlear organotypic cultures. The NK1 receptor was detected on SGNs by immunocytochemistry, the protein was detected in cochlear tissues by Western blots, and the mRNA for the NK1 receptor was also found in cochlear tissues of postnatal mice (P2) by RT-PCR. Application of SP (1 to 25 μM) significantly increased the latency of SGN action potentials (APs) (mean increase 7.8±4 ms; 25 μM of SP), prolonged the duration of the action potential and made the resting potential (RP) more positive (mean 9.0±7 mV) relative to normal values (-54±6 mV). SP (1 to 25 μM) also suppressed voltage-activated potassium currents (I_K+) and calcium currents (I_Ca2+). Puffing 25 μM of SP onto SGNs suppressed I_K+ by 43±9% (n=7) and I_Ca2+ by 40.6±5.6% (n=7); both currents recovered when SP was washed out. A SP antagonist blocked the SP-induced suppression of I_K+ and I_Ca2+. These results indicate that SP acting through NK1 receptors can have direct neuromodulatory effects on SGNs.