The Journal of neuroscience : the official journal of the Society for Neuroscience
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Spontaneous activity driven by "pacemaker" neurons, defined by their intrinsic ability to generate rhythmic burst firing, contributes to the development of sensory circuits in many regions of the immature CNS. However, it is unknown whether pacemaker-like neurons are present within central pain pathways in the neonate. Here, we provide evidence that a subpopulation of glutamatergic interneurons within lamina I of the rat spinal cord exhibits oscillatory burst firing during early life, which occurs independently of fast synaptic transmission. ⋯ The activation of high-threshold (N-type and L-type) voltage-gated Ca(2+) channels also facilitated rhythmic burst firing by triggering intracellular Ca(2+) signaling. Bursting neurons received direct projections from high-threshold sensory afferents but transmitted nociceptive signals with poor fidelity while in the bursting mode. The observation that pacemaker neurons send axon collaterals throughout the neonatal spinal cord raises the possibility that intrinsic burst firing could provide an endogenous drive to the developing sensorimotor networks that mediate spinal pain reflexes.
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A-kinase anchoring protein 150 (AKAP150) is a scaffolding protein that controls protein kinase A- and C-mediated phosphorylation of the transient receptor potential family V type 1 (TRPV1), dictating receptor response to nociceptive stimuli. The phospholipid phosphatidylinositol-4,5-bisphosphate (PIP(2)) anchors AKAP150 to the plasma membrane in naive conditions and also affects TRPV1 activity. In the present study, we sought to determine whether the effects of PIP(2) on TRPV1 are mediated through AKAP150. ⋯ Phospholipase C activation in neurons isolated from AKAP150(-/-) animals indicated that PIP(2)-mediated inhibition of TRPV1 in the whole-cell environment requires expression of the scaffolding protein. Furthermore, the addition of PIP(2) to neurons isolated from AKAP150 wild-type mice reduced PKA sensitization of TRPV1 compared with isolated neurons from AKAP150(-/-) mice. These findings suggest that PIP(2) degradation increases AKAP150 association with TRPV1 in the whole-cell environment, leading to sensitization of the receptor to nociceptive stimuli.