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 Ca2+ entry. We used high-speed optical recording techniques to study the effects of selectively inhibiting D-current with 4-AP (40 microM) 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 Ca(2+)-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.
Barish
M E
ME
Section of Cellular and Molecular Neuroscience, Electrotechnical Laboratory, Ibaraki, Japan.
Ichikawa
M
M
Tominaga
T
T
Matsumoto
G
G
Iijima
T
T
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004594:Electrophysiology; D018756:GABA Antagonists / Q000494:pharmacology; D005973:Glutamine / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008839:Microelectrodes; D055095:Optics and Photonics; D011188:Potassium / Q000037:antagonists & inhibitors* / Q000502:physiology; D017729:Presynaptic Terminals / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D018756:GABA Antagonists; D005973:Glutamine; D005680:gamma-Aminobutyric Acid; D015761:4-Aminopyridine; D011188:Potassium; D001640:Bicuculline