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.