Cell-type specific depression of neuronal excitability in rat hippocampus by activation of ATP-sensitive potassium channels

Abstract.

The contribution of ATP-sensitive potassium (K_ATP) channels to neuronal excitability was studied in different types of pyramidal cells and interneurones in hippocampal slices prepared from 9- to 15-day-old rats. The presence of functional K_ATP channels in the neurones was detected through the sensitivity of whole-cell currents to diazoxide, a K_ATP channel opener, and to tolbutamide, a K_ATP channel inhibitor. The percentages of neurones with K_ATP channels increase in the sequence: CA1 pyramidal cells (37%)<<CA3 pyramidal cells (86%)≈CA1 interneurones of the stratum radiatum (87%)<CA1 interneurones of the stratum oriens (92%). Activation of K_ATP channels by diazoxide strongly hyperpolarized stratum radiatum interneurones by a mean of –18.6 mV and effectively suppressed spontaneous and induced action potentials. Pyramidal cells containing a lower density of K_ATP channels were hyperpolarized by diazoxide by only –4.0 mV (CA1) and –7.9 mV (CA3), and the frequencies of spontaneous and induced action potentials decreased less than in interneurones. All effects of diazoxide were reversed by tolbutamide. Our results show that K_ATP channels have profound effects on the excitability of hippocampal neurones and imply that channel activation during ischaemia or hypoxia depresses the activities of excitatory pyramidal cells to a much lesser extent than those of inhibitory interneurones. This distinct cell-type specific depression of neuronal excitability could account for the generation of seizures and the selective neuroprotection of interneurones in the hippocampus during periods of energy depletion.