Kainate induces an intracellular Na+-activated K+ current in cultured embryonic rat hippocampal neurones

摘要

class="enumerated" style="list-style-type:decimal">In embryonic rat hippocampal neurones cultured for < 3 days, kainate induced an inward current at negative potentials that recovered to baseline levels immediately upon termination of agonist application. However, in neurones cultured for longer, the kainate-induced current was often followed by a long-lasting inward current that slowly recovered to baseline levels. The amplitude of the delayed current (Idelay) triggered by kainate was positively related both to the duration of application at constant agonist concentration and to concentration at constant application duration.Idelay could last for several minutes and was accompanied by a conductance increase, which closely paralleled current amplitude. Depression of the kainate-induced current response at receptor level with CNQX or at ionic level with Na⁺-free solution eliminated Idelay. However, when applied during Idelay neither CNQX nor Na⁺-free solution had any effect on Idelay. Li⁺ effected the same response as Na⁺ in mediating kainate-induced Idelay.GABA-activated Cl⁻ current, which was associated with the same amount of inwardly directed charge flow at the same potential as that induced by kainate, did not trigger a long-lasting delayed current.Idelay depended on the existence of extracellular K⁺ and its amplitude increased with the increase in K⁺ concentration. Neither applying Cl⁻- or Ca²⁺-free solutions nor increasing intracellular Ca²⁺ buffering speed and capacity altered Idelay. Exposure to the specific KCa channel blockers apamin and charybdotoxin also failed to alter Idelay. However, Idelay could be blocked by Cs⁺, Ba²⁺ and high concentrations of 4-aminopyridine (4-AP) and TEA.Inside-out excised patch-clamp recordings revealed that low density or highly clustered Na⁺-activated K⁺ channels were expressed in the cell bodies of cultured embryonic rat hippocampal neurones. These could be the elementary channels underlying Idelay.