ENHANCED FAST SYNAPTIC TRANSMISSION AND A DELAYED DEPOLARIZATION-INDUCED BY TRANSIENT POTASSIUM CURRENT BLOCKADE IN RAT HIPPOCAMPAL SLICE AS STUDIED BY OPTICAL-RECORDING

In hippocampal neurons, a slowly inactivating aminopyridine-sensitive transient potassium current, D-current, influences the time course of action potential repolarization and therefore activity-dependent Ca2entry. We used high-speed optical recording techniques to study the ef fects of selectively inhibiting D-current with 4-AP (40 mu M) on trans mission at the Schaffer collateral (CA3)-CA1 synapse in rat hippocampa l slices stained with the voltage-sensitive dye RH-155. We observed th at addition of 4-AP to the bathing solution resulted in (1) augmentati on of a last component of the optical signal corresponding to the post synaptic EPSP and action potential, and (2) the appearance of a delaye d depolarization of CA1 neurons and other adjacent cells. 4-AP appeare d to alter the presynaptic action potential and the dynamics of synapt ic transmission to both reduce the sensitivity of the postsynaptic EPS P and action potential to omega-toxin calcium channel blockers (omega- conotoxin GVIA and omega-agatoxin IVA) and the Ca2+-dependent potassiu m channel blocker charybdotoxin, and to increase sensitivity to the di hydropyridine nifedipine, the NMDA receptor blocker aminophosphonopent anoic acid, and the intracellular Ca2+ release inhibitor thapsigargin. The delayed depolarization induced by 4-AP was inhibited in hyperosmo tic extracellular solution, suggesting that enhanced transmitter relea se resulted in increased accumulation of K+ in the extracellular space , Because 4-AP is a convulsant at concentrations similar to those used here, we suggest that the 4-AP-targeted channel(s) carrying D-current may contribute to the hyperexcitability associated with epilepsy.