Ca-independent augmentation of endplate potential during repetitive stimulation

To elucidate the role of intracellular Ca ions in neuromuscular transmission, we investigated using frog neuromuscular preparations the effect of 1,2-bis(o-aminophenoxy)ethane- N,N,N',N'-tetraacetic acid (BAPTA) on frequency augmentation-potentiation (formerly frequency facilitation), which have been shown to be useful in identifying the sites of actions of various cholinergic agents. Buffering of intracellular Ca ions by BAPTA was found to suppress only Ca-dependent component of frequency augmentation-potentiation (mo); its stimulation frequency dependent factor (k) remained unaffected. Depression by BAPTA treatment of the short-term facilitation of endplate potential (EPP) was the same in both the resting and augmented states. However, the effect of BAPTA was antagonized, but only partially, with the administration of Ca-ionophore, A23187. These suggest that Ca-buffering capability of the intracellularly loaded BAPTA was maintained during low frequency repetitive stimulation. In addition, the post-tetanic potentiation of miniature EPP frequency in Ca-free EGTA Ringer was practically unaffected with BAPTA treatment. Undoubtedly Ca ions were essential for transmitter release and short-term facilitation, but Ca ions were not solely responsible for all the changes of transmitter release. The contribution of transmitter mobilization to maintaining the synaptic transmission during repetitive stimulation should be reevaluated.