SUMMARY Daily electrical stimulation of the amygdala caused a progressive change in electrographic afterdischarge and behavioral responses that ultimately resulted in generalized convulsions (kindling). Cycloheximide blocked the completion of kindling when administered 4 hours prior to daily electrical stimulations of the amygdala, but exerted no effect when administered shortly before the stimulation. The temporal relation between administration of cycloheximide and stimulation of the amygdala revealed that the blockade of kindling by cycloheximide was due to the suppression of focal afterdischarge rather than to the persistent inhibition of cerebral protein synthesis during the interstimulus periods. RÉSUMÉ La stimulation électrique quotidienne de l'amygdale causait une modification progressive de la post‐decharge et des réponses comportementales aboutis‐sant finalement a des convulsions généralisées (phenomene d'embrasement ou kindling). La cycloheximide bloquait le phénomene d'embrasèment lorsqu'elle était administerée 4 heures avant la stimulation quotidienne de l'amygdale, mais n'avait pas d'effet si l' administration précédait de peu la stimulation. La relation chronologique entre 1'administration de cycloheximide et la stimulation de l'amygdale montrait que le blocage de l' embrasement par la cycloheximide était du à la suppression de la postdécharge focale plutôt qu'à l' inhibition per‐manente de la synthèse des protéïnes pendant les in‐tervalles de stimulation. RÉSUMÉN La estimulación diaria de la amigdala causó un cam‐bio progresivo de la postdescarga electrografica y de las respuestas de comportamiento que, finalmente, condujo a convulsiones generalizadas (kindling). La cicloheximida bioquea el kindling cuando se ad‐ministra 4 horas antes de la estimulacion eléctrica diaria de la amígdala, pero no ejerce ningun efecto cuando se administra inmediatamente antes de la estimulación. La relación temporal entre la administra‐cion de la cicloheximida y la estimulación de la amigdala reveló que el bloqueo del kindling por la cicloheximida era debido a la supresión de las postdescargas focales y no a la inhibición persistente de la sintesis de proteinas cerebrales que tiene lugar durante los periodos interestimulo. ZUSAMMENFASSUNG Täglich elektrische Stimulation der Mandelkerne rief eine allmählich zunehmende Veränderung der elektrischen Nachentladung und des Verhaltens hervor. die schließlich in generalisierten Krampfen mundétén (Kindling). Cycloheximid blockierte das Kindlingphanomen wenn die Substanz 4 Stunden vor der täglichen elektrischen Stimulation verabfolgt wurde; die Wirkung fehlte, wenn die Gabe kurz vor der Stimulation erfolgte. Die zeitlichen Beziehungen zwischen der Verabfolgung von Cycloheximid und der Mandelkernstimulation zeigten, daß die Unterdrück‐ung der fokalen Nachentladung als Folge einer Verhinderung der cerebralen Proteinsynthese während der Perioden zwischen der Stimulation ist.
Properties of membrane K+ conductances induced by baclofen and gamma-aminobutyric acid (GABA) in the hippocampus were investigated by using guinea-pig brain slices. Baclofen hyperpolarized the membrane and decreased the input resistance of pyramidal cells through the activation of a membrane K+ conductance. GABA caused a biphasic response in pyramidal cells, consisting of hyperpolarizing and depolarizing components. Combined application of picrotoxin and bicuculline eliminated the major part of the depolarizing component of the biphasic response and produced a relatively pure hyperpolarizing response which was also mediated by an increase in K+ conductance. The K+ conductance change induced by baclofen showed prominent inward rectification. However, the K+ conductance induced by GABA did not show an obvious rectifying property. The K+ conductance activated by baclofen was strongly antagonized by a low concentration (5 x 10(-6) M) of 4-aminopyridine (4-AP). In contrast, the K+ conductance activated by GABA was insensitive to 4-AP even at a high concentration of 10(-3) M. The slow inhibitory postsynaptic potential (slow i.p.s.p.) evoked by stimulation of the mossy fibres was totally suppressed by a low concentration of baclofen (5 x 10(-6) M). Whereas GABA (10(-3) M) decreased the amplitude of the slow i.p.s.p., the reduction of the amplitude was proportional to the decrease in the amplitude of the electrotonic potentials produced by constant inward current injections. These results suggest that the hyperpolarizations induced by GABA and baclofen may be generated by K+ conductances of different kinetic and pharmacologic properties.
Recent studies on the voltage-gated Na+ channel (VGSC) have revealed several excellent discoveries regarding its structure and function. This article summarizes recent findings on VGSCs, and presents our views on the subject. Based on the multi-pore 3D model of the VGSC, we propose a ”twist-sprinkler“ model: (i) twisting and untwisting of the central cavity corresponds to the closed and open states of the channel, and (ii) cytoplasmic outlet pores sprinkle Na+ ions laterally over the inner surface of the plasma membrane to effect a rapid depolarization. VGSCs can be classified into two major categories. Category-I isoforms currently comprise nine highly homologous clones (Nav1.1- Nav1.9), most of which have been functionally expressed. In contrast, the category-II isoform consists of one clone (Nax), which has not been successfully expressed in an exogenous system. It is considerably different from the category-I isoforms, especially in the S4 segment, and shows little voltage dependence. The main function of the category-I isoforms is to form an action potential upstroke. However, NaV1.6 can also influence subthreshold electrical activity in neurons through the ”persistent“ and ”resurgent“ Na+ currents, indicating that the VGSC itself can modulate overall neuronal firing behavior. NaV1.8 and NaV1.9 are preferentially expressed in peripheral nociceptive neurons and contain a structure common to tetrodotoxin (TTX)-resistant Na+ channels. Both Nav1.8 and Nav1.9 play a pivotal role in pain sensation. The category-II isoform Nax (x = unknown function) is a ”concentration-sensitive“ but not ”voltage-sensitive“ Na+ channel. It is involved in regulation of salt intake behavior by sensing an increase in [Na+]o, and it should be renamed as Nac (c = concentration). Keywords: Na Channel, Multigene Family, INFLAMMATORY PAIN
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