It has been generally assumed that the cell body (soma) of a neuron, which contains the nucleus, is mainly responsible for synthesis of macromolecules and has a limited role in cell-to-cell communication. Using sniffer patch recordings, we show here that electrical stimulation of dorsal root ganglion (DRG) neurons elicits robust vesicular ATP release from their somata. The rate of release events increases with the frequency of nerve stimulation; external Ca 2؉ entry is required for the release. FM1-43 photoconversion analysis further reveals that small clear vesicles participate in exocytosis. In addition, the released ATP activates P2X7 receptors in satellite cells that enwrap each DRG neuron and triggers the communication between neuronal somata and glial cells. Blocking L-type Ca 2؉ channels completely eliminates the neuron-glia communication. We further show that activation of P2X7 receptors can lead to the release of tumor necrosis factor-␣ (TNF␣) from satellite cells. TNF␣ in turn potentiates the P2X3 receptor-mediated responses and increases the excitability of DRG neurons. This study provides strong evidence that somata of DRG neurons actively release transmitters and play a crucial role in bidirectional communication between neurons and surrounding satellite glial cells. These results also suggest that, contrary to the conventional view, neuronal somata have a significant role in cell-cell signaling.neuron-glia communication ͉ somatic release ͉ P2X3 ͉ P2X7 ͉ tumor necrosis factor ␣ N eurons use transmitters released from vesicles at presynaptic terminals to communicate with other cells (1). Recent reports suggest that transmitter release also takes place in extrasynaptic domains (ectopic release) (2). It has been assumed for a long time that the cell body (i.e., soma) of a neuron does not release transmitters in response to electrical stimulation. This assumption has been challenged by our and others' observations that neuronal somatic release indeed occurs (3-10). Using carbon fibers, several groups have shown that somatic release of catecholamine occurs through vesicular mechanisms (3, 5-7). Exocytosis in response to membrane depolarization has also been reported in the somata of dorsal root ganglion (DRG) neurons (4), a group of neurons responsible for transmitting touch, temperature and pain information from the periphery to the spinal cord (11). In most cases, soma release is triggered and enhanced by voltage-dependent Ca 2ϩ channels (4-7, 10). Despite these studies, it is not known whether vesicular release of fast-acting transmitters, e.g., ATP or glutamate, occurs in the somata. The function of somatic release is poorly understood.ATP has been shown to be released from nerve terminals and axons of DRG neurons (12, 13), and is involved in synaptic transmission at afferent-dorsal horn synapses (14) and neuron-glia signaling (15). Because ATP-activated P2X receptors become greatly sensitized after injury (16-19), ATP is a transmitter especially important for signaling injurious nociceptive informat...

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