Neurones were isolated from the hippocampus of adult guinea-pigs by enzymatic and mechanical treatment. The electrophysiological properties of these cells were examined immediately after dissociation by intracellular recordings using low-resistance electrodes (2-5 M omega). 2. Pyramidal-shaped cells were identified visually. Intracellular recordings showed that these cells have input resistances ranging from 200 to 1300 M omega. Passive voltage responses to hyperpolarizing current injection were fitted by single exponentials decaying with time constants ranging from 15 to 60 ms. This suggests that the electrotonic structure of these cells is compact such that injected current elicited isopotential intracellular responses. 3. Outward currents activated by depolarization were examined in these cells using voltage-clamp techniques. The amplitude and the time course of the outward currents were profoundly affected by the holding potential. For cells held at -50 mV or more positive, depolarizing steps produced a slowly rising outward current. At holding potentials negative to -55 mV depolarizing pulses produced an additional early transient outward current followed by a slowly rising component which decayed gradually during sustained depolarizations. 4. The outward currents were separated by their kinetic properties and their sensitivity to cobalt (Co2+), tetraethylammonium (TEA) and 4-aminopyridine (4-AP). 5. The transient current peaked within 6 ms of the onset of depolarizing pulses. It decayed exponentially with a time constant of 20-40 ms. The amplitude of the current activated by a fixed depolarization increased gradually as the duration or the amplitude of the hyperpolarizing pre-pulse increased. The current activated by a fixed depolarization reached its half-maximal level when the hyperpolarizing pre-pulse was at -83 mV. 6. 4-AP exerted two actions on the transient current. Firstly, the time constant of the falling phase decreased by about a factor of two. Secondly, the current was blocked in a time- and voltage-dependent manner: the block increased when the hyperpolarizing pre-pulse lengthened. TEA, up to 10 mM, did not affect the amplitude of the transient current. Co2+ suppressed this current. The effects of Co2+ consisted of a shift to the positive direction of the voltage dependence of the current. 7. The delayed currents can be divided into Ca2+-dependent and Ca2+-independent components. The component persistent in the Co2+ solution (K-current) decayed slowly with maintained depolarization (time constant greater than 3 s).(ABSTRACT TRUNCATED AT 400 WORDS)
