Li+ and muscarine cooperatively enhance the cationic tail current in rat cortical pyramidal cells.
Li+ is known to facilitate the onset of status epilepticus induced by cholinergic stimulation, although the underlying mechanisms are not clear. Under whole-cell current clamp conditions with a CsCl-based internal solution, cortical pyramidal cells display a single plateau-spike followed by a slow depolarizing afterpotential (DAP) in response to injection of a short current pulse. However, the same current pulse generated a burst of plateau-spikes after application of Li+ (2 mM) and muscarine (10 microM). As similar bursts of plateau-spikes were generated through an enhancement of the slow DAP when [K+]o was raised (Kang et al. 1998), we have investigated the effects of Li+ and muscarine on the Ca2+-dependent cationic current underlying the slow DAP, measured as the slow tail current evoked after the offset of depolarizing voltage pulses. Muscarine enhanced the amplitudes of both early and late components of the slow tail current. This effect of muscarine was markedly potentiated by Li+, while Li+ by itself affected the slow tail current only slightly. Intracellular application of heparin (0.5-1 mg/mL) suppressed the effect of muscarine in the presence of Li+. These results suggest that inositol-trisphosphate-induced Ca2+ release is involved in the cooperative enhancement of the slow tail current, and this cooperation may be one of the mechanisms underlying facilitation of the onset of epilepsy induced by these agents.
Okada
T
T
Department of Physiology, Faculty of Medicine, Kyoto University, 606 Japan.
Kang
Y
Y
Ohmori
H
H
D000818:Animals; D002412:Cations / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004357:Drug Synergism; D004553:Electric Conductivity; D006493:Heparin / Q000494:pharmacology; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology*; D009116:Muscarine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002412:Cations; D009116:Muscarine; D006493:Heparin; D008094:Lithium