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Volume 16, Number 18, Issue of September 15, 1996 pp. 5672-5687
Copyright ©1996 Society for Neuroscience

Enhanced Fast Synaptic Transmission and a Delayed Depolarization Induced by Transient Potassium Current Blockade in Rat Hippocampal Slice as Studied by Optical Recording

Received Dec. 26, 1995; revised June 24, 1996; accepted June 26, 1996.

Michael E. Barish, Michinori Ichikawa, Takashi Tominaga, Gen Matsumoto, and Toshio Iijima

Section of Cellular and Molecular Neuroscience, Electrotechnical Laboratory, Tsukuba, Ibaraki 305, Japan

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 Ca2+ entry. We used high-speed optical recording techniques to study the effects of selectively inhibiting D-current with 4-AP (40 µ) on transmission at the Schaffer collateral (CA3)-CA1 synapse in rat hippocampal slices stained with the voltage-sensitive dye RH-155. We observed that addition of 4-AP to the bathing solution resulted in (1) augmentation of a fast component of the optical signal corresponding to the postsynaptic EPSP and action potential, and (2) the appearance of a delayed depolarization of CA1 neurons and other adjacent cells. 4-AP appeared to alter the presynaptic action potential and the dynamics of synaptic transmission to both reduce the sensitivity of the postsynaptic EPSP and action potential to omega -toxin calcium channel blockers (omega -conotoxin GVIA and omega -agatoxin IVA) and the Ca2+-dependent potassium channel blocker charybdotoxin, and to increase sensitivity to the dihydropyridine nifedipine, the NMDA receptor blocker aminophosphonopentanoic acid, and the intracellular Ca2+ release inhibitor thapsigargin. The delayed depolarization induced by 4-AP was inhibited in hyperosmotic extracellular solution, suggesting that enhanced transmitter release 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.

Key words: hippocampus; optical recording; microelectrode recording; voltage-gated potassium current; A-current; D-current; 4-aminopyridine; RH-155; RH-482; epilepsy




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