Substance P elevates intracellular calcium in both neurons and glial cells from the dorsal horn of the spinal cord

Abstract

1. We used microfluorimetric measurement of [Ca2+]i to identify substance P-sensitive cells acutely isolated from the dorsal horn of neonatal rats. We then used morphological, physiological, and immunocytochemical criteria to delineate two distinct populations of substance P-sensitive dorsal horn cells. 2. One population of cells with small-diameter cell bodies and many fine processes responds to substance P by releasing Ca2+ from internal stores. Many of these cells express the O4 surface antigen, and are thus likely to be glial cells, probably from the oligodendrocyte lineage. None of the cells with glial attributes respond to N-methyl-D-aspartate (NMDA), providing further evidence that they are nonneuronal. 3. In a second population of dorsal horn cells, substance P elevates [Ca2+]i by promoting Ca2+ entry. This class of cells is morphologically distinct from substance P-sensitive glial cells in that it exhibits large-diameter cell bodies, has smooth tapering processes, and is sensitive to NMDA. This second class of cells is therefore likely to consist of neurons. 4. Consistent with the identification of different mechanisms of Ca2+ elevation in the two cell types, the kinetics of the substance P-evoked release of Ca2+ in glial cells is very different than the kinetics of the Ca(2+)-entry response evoked in neurons. The glial cell response had a rapid average rate of rise (mean = 260 +/- 105 nM/s) and relatively brief duration (mean = 7.6 +/- 2.2 s) whereas the neuronal response had a much slower rate of rise (mean = 10 +/- 9 nM/s) with a much longer duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium Calmodulin-Stimulated Adenylyl Cyclases Contribute to Activation of Extracellular Signal-Regulated Kinase in Spinal Dorsal Horn Neurons in Adult Rats and Mice

“…SP plays dual roles in spinal nociceptive transmission as a transmitter of primary afferent fibers and a modulator of local and descending pathways. It is known that the activation of the NK1 receptor increases intracellular calcium concentrations (Shen and North, 1992;Otsuka and Yoshioka, 1993;Heath et al, 1994). In the present study, we found that SP activated Erk in spinal dorsal horn neurons, and a selective NK1 receptor antagonist could block the effect of SP.…”

ATP P2XReceptors Mediate Fast Synaptic Transmission in the Dorsal Horn of the Rat Spinal Cord

“…Ca 2ϩ imaging with the Ca 2ϩ indicator dye fura-2 (Grynkiewicz et al, 1985) was used to perform the pharmacological testing because it provides a way to scan rapidly a field of neurons and to detect the minority of cells sensitive to ATP. Neuronal identity was confirmed by morphology and sensitivity to 100 M NMDA (Heath et al, 1994). E xogenously applied ATP (100 M) elevated intracellular Ca 2ϩ concentration ([C a 2ϩ ] i ) in a small subpopulation (Ͻ5%) of acutely dissociated dorsal horn neurons (Fig.…”

Resistance to excitotoxin-induced seizures and neuronal death in mice lacking the preprotachykinin A gene

“…These findings indicate that SP could be involved in a seizure-induced cell death pathway involving bax and caspases. SP, while increasing intracellular Ca 2ϩ (6) and enhancing glutamate responses (7,8) or glutamate release (9,38), may induce expression and activation of bax (39) and caspase 3 (31). Activation of bax may trigger the release of cytochrome c and other proteins from the mitochondria and induce caspase activation in cytosol (26,27).…”