A phenytoin-sensitive cationic current participates in generating the afterdepolarization and burst afterdischarge in rat neocortical pyramidal cells.
We report here on the ionic mechanisms underlying the depolarizing afterpotential (DAP) in neocortical pyramidal cells, with special interest in those underlying the burst afterdischarge. Injections of short depolarizing current pulses under whole-cell current clamp with a CsCl-based internal medium generated, in most pyramidal cells, a single action potential with a plateau phase (plateau-AP), followed by a slowly decaying DAP both in the absence and presence of TTX. Under voltage-clamp, the same cells displayed a slow tail current (tail-I) at the offset of depolarization. When intracellular free Ca2+ was chelated with 10 mM BAPTA or when extracellular Ca2+ was replaced with equimolar Ba2+, neither the slow DAP nor the slow tail-I was observed. Extracellular application of Co2+ or Cd2+ reduced Ca2+ currents and the slow tail-I. Cation substitution experiments revealed that the channel generating the slow tail-I was permeable to K+ and Cs+ more than to Na+ (PK is approximately equal to PCs > PNa > PNMDG is approximately equal to PTEA). The cationic slow tail-I was not reduced by applying antagonists of the metabotropic glutamate receptor (MCPG, 1 mM) and the muscarinic receptor (atropine, 1-10 microM). Thus, the slow DAP was produced by activation of the cationic channel whose gating is solely dependent on [Ca2+]i. An increase in [K+]o from 3 to 6 or 9 mM enhanced the slow DAP, and resulted in a generation of burst afterdischarges. An anticonvulsant, phenytoin (PT; 1-10 microM) suppressed the slow DAP while enhancing the plateau-AP in the presence of TTX, most likely by blocking the cationic channel.
Kang
Y
Y
Department of Physiology, Faculty of Medicine, Kyoto University, Japan. ykang@med.kyoto-u.ac.jp
Okada
T
T
Ohmori
H
H
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D019579:Neocortex / Q000166:cytology / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010672:Phenytoin / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016897:Respiratory Burst / Q000187:drug effects*
D000927:Anticonvulsants; D007473:Ion Channels; D010672:Phenytoin