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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 -toxin calcium channel
blockers ( -conotoxin GVIA and -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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