GTP MODULATES RUN-UP OF WHOLE-CELL CA2-DEPENDENT MANNER( CHANNEL CURRENT IN A CA2+)

1. Whole-cell voltage-clamp recordings were obtained from CAI neurons acutely dissociated from rat hippocampus to study the effects of guano sine 5'-triphosphate (GTP) on the gradual increase in Ca2+ channel cur rent amplitude that takes place over several minutes after breaking in to whole-cell mode (''run-up''). 2. Including GTP (500 mu M) in the p atch pipette significantly prolonged the duration of run-up of peak Ca 2+ channel current to its maximum value compared with controls without GTP when the recording solutions contained Ca2+. On the other hand, G TP significantly enhanced run-up when Mg2+ and Ba2+ were substituted f or intracellular and extracellular Ca2+, respectively. 3. The enhancem ent of run-up of the current in the Mg/Ba condition appeared to be due both to an initial increase in current amplitude that was complete wi thin 30 s after break in and to a more rapid initial rate of run-up wh en compared with the Ca2+ condition. GTP did not affect the absolute m aximum amplitudes of the currents in either Ca2+ or Ba2+ conditions. 4 . We conclude that an early GTP-dependent modulation of Ca2+ channel c urrent is qualitatively altered, depending on whether Ca2+ or Ba2+ is used as the charge carrier. Evidence of this modulation is apparent wi thin seconds after rupture of the membrane patch. Conceivably, influen ces occurring during the period of ''equilibration'' with electrode co ntents could alter subsequent regulatory steps.