title: Modulation of calcium currents and membrane properties by substance P in the lamprey spinal cord.
abstract: Substance P is endogenously released within the locomotor network of the adult lamprey, accelerates the burst frequency of fictive locomotion, and reduces the reciprocal inhibition. Previous studies have shown that dopamine, serotonin, and GABA regulate calcium channels, which control neurotransmitter release, action potential duration, and slow afterhyperpolarization (sAHP). Here we examine the effect of substance P on calcium channels in motoneurons and commissural interneurons using whole cell patch clamp in the lamprey spinal cord. This study analyzed the effects of substance P on calcium currents activated in voltage clamp. We examined the calcium-dependent sAHP in current clamp, to determine the involvement of three calcium channel subtypes modulated by substance P. The effects of substance P on membrane potential and during N-methyl-d-aspartic acid (NMDA) induced oscillations were also analyzed. Depolarizing voltage steps induced inward calcium currents. Substance P reduced the currents carried by calcium by 61% in commissural interneurons and by 31% in motoneurons. Using specific calcium channel antagonists, we show that substance P reduces the sAHP primarily by inhibiting N-type (Ca(V)2.2) channels. Substance P depolarized both motoneurons and commissural interneurons, and we present evidence that this occurs due to an increased input resistance. We also explored the effects of substance P on NMDA-induced oscillations in tetrodotoxin and found it caused a frequency increase. Thus the reduction of calcium entry by substance P and the accompanying decrease of the sAHP amplitude, combined with substance P potentiation of currents activated by NMDA, may both contribute to the increase in fictive locomotion frequency.
authors.affiliation: Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carolina Thörn
authors.initials: CT
authors.lastname: Pérez
authors.forename: Russell H
authors.initials: RH
authors.lastname: Hill
authors.forename: Sten
authors.initials: S
authors.lastname: Grillner
mesh_terms: D000818:Animals; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D007798:Lampreys; D008564:Membrane Potentials; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology*
chemical_list: D020864:Calcium Channels, N-Type; D013373:Substance P
keywords: calcium conductance; locomotor pattern generation; tachykinins