Action potential repolarization and a fast after‐hyperpolarization in rat hippocampal pyramidal cells.

1. The repolarization of the action potential, and a fast after‐hyperpolarization (a.h.p.) were studied in CA1 pyramidal cells (n = 76) in rat hippocampal slices (28‐37 degrees C). Single spikes were elicited by brief (1‐3 ms) current pulses, at membrane potentials close to rest (‐60 to ‐70 mV). 2. Each action potential was followed by four after‐potentials: (a) the fast a.h.p., lasting 2‐5 ms; (b) an after‐depolarization; (c) a medium a.h.p., (50‐100 ms); and (d) a slow a.h.p. (1‐2 s). Both the fast a.h.p. and the slow a.h.p. (but not the medium a.h.p.) were inhibited by Ca2+‐free medium or Ca2+‐channel blockers (Co2+, Mn2+ or Cd2+); but tetraethylammonium (TEA; 0.5‐2 nM) blocked only the fast a.h.p., and noradrenaline (2‐5 microM) only the slow a.h.p. This suggests that two Ca2+‐activated K+ currents were involved: a fast, TEA‐sensitive one (IC) underlying the fast a.h.p., and a slow noradrenaline‐sensitive one (IAHP) underlying the slow a.h.p. 3. Like the fast a.h.p., spike repolarization seems to depend on a Ca2+‐dependent K+ current of the fast, TEA‐sensitive kind (IC). The repolarization was slowed by Ca2+‐free medium, Co2+, Mn2+, Cd2+, or TEA, but not by noradrenaline. Charybdotoxin (CTX; 30 nM), a scorpion toxin which blocks the large‐conductance Ca2+‐activated K+ channel in muscle, had a similar effect to TEA. The effects of TEA and Cd2+ (or Mn2+) showed mutual occlusion. Raising the external K+ concentration reduced the fast a.h.p. and slowed the spike repolarization, whereas Cl‐ loading of the cell was ineffective. 4. The transient K+ current, IA, seems also to contribute to spike repolarization, because: (a) 4‐aminopyridine (4‐AP; 0.1 mM), which blocks IA, slowed the spike repolarization; (b) depolarizing pre‐pulses, which inactivate IA, had a similar effect; (c) hyperpolarizing pre‐pulses speeded up the spike repolarization; (d) the effects of 4‐AP and pre‐pulses persisted during Ca2+ blockade (like IA); and (e) depolarizing pre‐pulses reduced the effect of 4‐AP. 5. Pre‐pulses or 4‐AP broadened the spike less, and in a different manner, than Ca2+‐free medium, Cd2+, Co2+, Mn2+, TEA or CTX. The former broadening was uniform, with little effect on the fast a.h.p., whereas the latter affected mostly the last two‐thirds of the spike repolarization and abolished the fast a.h.p.(ABSTRACT TRUNCATED AT 400 WORDS)