Abstract
The specificity of action of Xestospongin C (XeC) towards the inositol 1,4,5-trisphosphate (IP 3) receptor has been studied using the frog neuromuscular junction. In perisynaptic Schwann cells (PSCs), glial cells at this synapse, Ca 2+ stores are dependent upon IP 3 activation. Bath application of XeC (700 nM) caused a transient calcium elevation and blocked Ca 2+ responses evoked in PSCs by synaptic activity or various agonists (ATP, muscarine, adenosine) only when Ca 2+ stores had previously been challenged with local application of agonists. Moreover, XeC occluded the effects of thapsigargin (tg; 2 μM), a blocker of the Ca 2+ ATPase pump of internal stores, which failed to evoke Ca 2+ transients following 20 min of exposure to XeC. In nerve terminals, where the Ca 2+ stores are ryanodine-sensitive, application of XeC (700 nM) prolonged the recovery phase of Ca 2+ transients evoked by single action potentials, due to a prolonged Ca 2+ clearance in the nerve terminal. No effects of tg (2 μM) were observed on Ca 2+ response evoked by nerve stimulation when applied on the preparation after XeC (700 nM). Conversely, XeC (700 nM) had no effect on the shape and duration of Ca 2+ entry in nerve terminals when tg was applied before XeC. These results indicate that XeC acts as an inhibitor of the sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase (SERCA) pump of internal stores.
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