Activation and desensitization of the caffeine-sensitive cation channels and calcium stores have no persistent effect on the electrophysiological properties of leech P neurones

In leech P neurones caffeine activates unselective ion channels in the plasma membrane and induces intracellular Ca²⁺ release (Schoppe, J., Hochstrate, P., Schlue, W.-R., 1997. Caffeine mediates cation influx and intracellular Ca²⁺ release in leech P neurones. Cell Calcium 22, 385–397). These effects are prominent only upon the first caffeine exposure, while subsequent applications are largely ineffective; i.e. both plasma membrane channels and intracellular Ca²⁺ release mechanism desensitize irreversibly. In order to examine whether this desensitization is paralleled by irreversible changes in the electrophysiological parameters of the cells, we investigated the action of caffeine on changes in membrane potential and the cytosolic free Ca²⁺ concentration, which were induced by varying the ionic composition of the extracellular fluid or by application of 5-hydroxytryptamine. Neither the resting values nor any of the experimentally induced shifts in membrane potential or cytosolic Ca²⁺ concentration were affected by caffeine, which suggests strongly that activation and/or desensitization of the caffeine-sensitive ion channels and Ca²⁺ stores have no long-lasting effect on the relevant electrochemical gradients, membrane conductances, or transport mechanisms.