Caffeine reduces the efficacy of electroreceptor cell synapses: an electrophysiological single-unit in vivo study

Ampullary electroreceptor organs of catfish, Ictalurus melas, were exposed apically to caffeine solutions at concentrations of 0, 5, 7.5, 10, and 15 mM. Recording sinusoidally-modulated activity of single-unit afferents reveals a dose-dependent decrease in mean afferent activity and sensitivity. A rebound effect of average activity occurs after caffeine is washed out. After 25 min exposure to 15 mM caffeine the peak of the gain curve shifts from 8 Hz to 4 Hz. The corresponding phase characteristic shows an increased phase lag with a maximum shift of 35 degrees at 20 Hz. The latency between stimulus and response increases from 12 to 19 ms; the recovery time after onset of the pulse decreases with 60 ms. The most probable explanation for the recorded effects is that caffeine reduces the availability of intracellular Ca2+ by blocking of the inositol triphosphate receptors in the endoplasmic reticulum. This in turn would affect many intracellular properties and processes. The unavailability of Ca2+ could reduce the synaptic efficacy and increase latency by suppressing fusion of synaptic vesicles with the presynaptic membrane and by depressing vesicle transport. The change in frequency response corresponds in part to reduction of the apical membrane surface area of the receptor cells, and in part to the increased latency. Accumulation of glutamate-containing vesicles could account for the higher mean activity and modulation amplitude in the lower frequency range after caffeine is washed out. Caffeine might act postsynaptically by inducing hyperpolarization of the terminals of the primary afferents.