Modulation of calcium currents and membrane properties by 4 substance P in the lamprey spinal cord

24 25 Substance P is endogenously released within the locomotor network of the adult lamprey, 26 accelerates the burst frequency of fictive locomotion and reduces the reciprocal 27 inhibition. Previous studies have shown that dopamine, 5-HT and GABA regulate 28 calcium channels, which control neurotransmitter release, action potential duration and 29 slow afterhyperpolarization. Here we examine the effect of substance P on calcium 30 channels in motoneurons and commissural interneurons using whole-cell patch clamp in 31 the lamprey spinal cord. This study analyzed the effects of substance P on calcium 32 currents activated in voltage clamp. We examined the calcium-dependent slow 33 afterhyperpolarization (sAHP) in current clamp, to determine the involvement of three 34 calcium channel subtypes modulated by substance P. The effects of substance P on 35 membrane potential and during NMDA induced oscillations were also analyzed. 36 Depolarizing voltage steps induced inward calcium currents. Substance P reduced the 37 currents carried by calcium by 61% in commissural interneurons and by 31% in 38 motoneurons. Using specific calcium channel antagonists we show that substance P 39 reduces the sAHP primarily by inhibiting N-type (Cav2.2) channels. Substance P 40 depolarized both motoneurons and commissural interneurons and we present evidence 41 that this occurs due to an increased input resistance. We also explored the effects of 42 substance P on NMDA-induced oscillations in TTX and found it caused a frequency 43 increase. Thus the reduction of calcium entry by substance P and the accompanying 44 decrease of the sAHP amplitude, combined with substance P potentiation of currents 45 activated by NMDA, may both contribute to the increase in fictive locomotion frequency. 46