The identification of a caffeine-induced Ca2+ influx pathway in rat primary sensory neurons.

Caffeine-induced Ca2+ transients (CICTs) in rabbit nodose ganglion neurons (NGNs) are produced by two distinct mechanisms: release from intracellular stores via ryanodine receptors and Ca2+ influx across the plasma membrane, due to activation of an unknown receptor. In isolated rat NGNs, we used single-cell microfluorimetry to measure changes in intracellular Ca2+ and to test whether TRPV1 receptors underlie the Ca2+ influx pathway. Caffeine (10 mM) evoked CICTs in all NGNs tested (n = 47) averaging 365 +/- 32 nM. CICTs were partially dependent upon a Ca2+ influx pathway that ranged between 33% and 98% of the total Ca2+ transient. Application of two selective TRPV1 antagonists significantly attenuated CICTs. The peak average amplitudes of CICTs in Ca2+-free Locke solution and Ca2+-free Locke solution with IRTX or with BCTC were not significantly different from one another (n = 5 and 7, respectively). These observations suggest that caffeine can induce Ca2+ influx by activating TRPV1 channels.