The chemokine interleukin-8 acutely reduces Ca2+ currents in identified cholinergic septal neurons expressing CXCR1 and CXCR2 receptor mRNAs

The chemokine IL-8 is known to be synthesized by glial cells in the brain. It has traditionally been shown to have an important role in neuroinflammat ion but recent evidence indicates that it may also be involved in rapid sig naling in neurons. We investigated how IL-8 participates in rapid neuronal signaling by using a combination of whole-cell recording and single-cell RT -PCR on dissociated rat septal neurons. We show that IL-8 can acutely reduc e Ca2+ currents in septal neurons, an effect that was concentration-depende nt, involved the closure of L- and N-type Ca2+ channels, and the activation of G(i alpha1) and/or G(i alpha2) subtype(s) of G-proteins. Analysis of th e mRNAs from the recorded neurons revealed that the latter were all choline rgic in nature. Moreover, we found that all cholinergic neurons that respon ded to IL-8, expressed mRNAs for either one or both IL-8 receptors CXCR1 an d CXCR2. This is the first report of a chemokine that modulates ion channel s in neurons via G-proteins, and the first demonstration that mRNAs for CXC R1 are expressed in the brain. Our results suggest that IL-8 release by gli al cells in vivo may activate CXCR1 and CXCR2 receptors on cholinergic sept al neurons and acutely modulate their excitability by closing calcium chann els.