Hyperpolarizing potentials in guinea pig hippocampal CA3 neurons

1. There is a bewildering variety of hyperpolarizing potentials which control activity in hippocampal pyramidal cells. These include an inhibitory postsynaptic potential (IPSP) with early and late components, voltage- and calcium-dependent potassium conductances, a voltage-dependent potassium conductance modulated by muscarinic agents (the M-current), and a complex and poorly understood afterhyper-polarization following epileptiform bursts. 2. In hippocampal CA3 pyramidal cells, mossy fiber stimulation elicits an IPSP which is made up of two readily separable components. Using the in vitro slice preparation, we investigated the underlying ionic basis of these IPSP components and compared them to other hyperpolarizing potentials characteristic of the CA3 neurons. 3. Intracellular recordings were obtained and then tissue was exposed to bathing medium low in chloride concentration or high in potassium concentration; the ion "blockers" EGTA (intracellular); tetraethylammonium (TEA) (intra- and extracellular), and barium and cobalt (extracellular); and the γ-aminobutyric acid (GABA)/ chloride antagonists penicillin, bicuculline and picrotoxin. 4. As has been reported by others, the early part of the CA3 IPSP is a GABAergic, chloride-dependent potential generated at proximal (probably somatic) membrane. The later component of the IPSP is a potassium-dependent synaptic potential, which is picrotoxin and bicuculline insensitive, not dependent on increases in intracellular calcium, and apparently produced on distal (dendritic) membranes. 5. The later component of the IPSP is clearly different from the calcium-dependent potassium conductance [g_K(Ca)] responsible for hyperpolarizations following normal spontaneous and current-induced burst discharge in hippocampal pyramidal cells. The late component of the IPSP may have some similarities to the afterhyperpolarization seen following penicillin-induced burst discharges.