Some effects of procaine at the toad end-plate are not consistent with a simple channel-blocking model

Miniature end-plate currents (m.e.p.c.s) were recorded extracellularly from toad sartorius muscle fibres exposed to solutions containing procaine at pH 5.4, 7.4 and 9.9. The decay phase of m.e.p.c.s was analysed to determine whether the effects of procaine were consistent with a sequential channel-blocking model. Averaged m.e.p.c.s measured in the presence of procaine were biphasic, decaying as the sum of two exponential components. However, about 10-15% of m.e.p.c.s decayed as single exponentials and were not biphasic. At pH 9.9 the relative amplitudes of the fast and slow phases were generally consistent with the decay time constants, according to the predictions of the blocking model. Such a correlation was not found at pH 5.4 or 7.4. In addition, the rate of decay of m.e.p.c.s at pH 5.4 did not increase as predicted with procaine concentration. These results demonstrate that the sequential blocking model is unable to account for all of the effects of procaine on m.e.p.c. decay. In addition, the finding that some m.e.p.c.s are single exponentials, while most are biphasic, suggests a heterogeneity of receptor-channel complexes.