The signaling cascade involved in chemosensory transduction in the VN organ is incompletely understood. In snakes, the response to nonvolatile prey chemicals is mediated by the vomeronasal (VN) system. Using optical techniques and fluorescent Ca(2+) indicators, we found that prey-derived chemoattractants produce initially a transient cytosolic accumulation of [Ca(2+)](i) in the dendritic regions of VN neurons via two pathways: Ca(2+) release from IP(3)-sensitive intracellular stores and, to a lesser extent, Ca(2+) influx through the plasma membrane. Both components seem to be dependent on IP(3) production. Chemoattractants evoke a short-latency Ca(2+) elevation even in the absence of extracellular Ca(2+), suggesting that in snake VN neurons, Ca(2+) release from intracellular stores is independent of a preceding Ca(2+) influx, and both components are activated in parallel during early stages of chemosensory transduction. Once the response develops in apical dendritic segments, other mechanisms can also contribute to the amplification and modulation of these chemoattractant-mediated cytosolic Ca(2+) transients. In regions close to the cell bodies of the VN neurons, the activation of voltage-sensitive Ca(2+) channels and a Ca(2+)-induced Ca(2+) release from intracellular ryanodine-sensitive stores secondarily boost initial cytosolic Ca(2+) elevations increasing their magnitude and durations. Return of intracellular Ca(2+) to prestimulation levels appears to involve a Ca(2+) extrusion mediated by a Na(+)/Ca(2+) exchanger mechanism that probably plays an important role in limiting the magnitude and duration of the stimulation-induced Ca(2+) transients.