1. Whole-cell patch-clamp techniques were used to record outward currents in embryonic rat neocortical neurons maintained in culture. In the presence of tetrodotoxin and cadmium, depolarization evoked an outward current with a complex waveform. This outward current consisted of an initial fast transient component and a late, slowly inactivating component. 2. The two outward current components could be separated pharmacologically with the use of tetraethylammonium (TEA) and 4-aminopyridine (4-AP). TEA (20 mM) applied extracellularly completely blocked the late component, unmasking a fast transient outward current (TOC). 4-AP (5 mM) applied extracellularly blocked the early component while reducing the late component by 27.8 ± 9.7% (mean ± SE). 3. The TOC activated after a short delay and rose rapidly to a peak. The time to peak was voltage dependent and decreased with depolarization. In the presence of 200 μM extracellular cadmium, activation threshold was around 25 mV, and current amplitude increased with depolarization. The voltage-conductance relationship was well fitted by the use of the Boltzmann equation with a V(m) of +19 mV for half activation and a slope factor of +6 mV. 4. On sustained depolarization the TOC rapidly inactivated and decayed to baseline within 500-600 ms. The decay phase followed a single exponential time course with a time constant of 55-65 ms. The decay time was most rapid at potentials from +5 to +20 mV and increased slightly with further depolarization. 5. Steady-state inactivation of the TOC, in the presence of cadmium, was complete near -10 mV and was totally relieved at potentials more negative than -75 mV. With the use of the Boltzmann equation, a V(m) of 34 mV for half inactivation and a slope factor of -8.6 mV were found. 6. Recovery of the TOC from steady-state inactivation followed a single exponential time course and was voltage dependent. When the membrane potential was held at -84 mV during the conditioning pulse, the time constant of recovery was 17 ms, increasing to 45.2 and 58.1 ms at holding potentials of -64 and -44 mV, respectively. Holding at potentials more negative than -84 mV produced no further change in the recovery time course. 7. The presence of 200 μM external cadmium altered the TOC activation and inactivation curves. Removal of cadmium produced a -16-mV shift in the V(m) for half activation and a -25- mV shift in the inactivation curve. This sensitivity to cadmium is higher than that reported in other systems. 8. These results indicate that depolarization of cultured rat neocortical neurons produces an outward current that is pharmacologically similar to the TOC, or A-current, seen in other types of mammalian neurons. The kinetics of this current differ from those previously described and suggest that this current could play a role in action-potential repolarization or inhibition of voltage-gated calcium currents.
