Inhibition of slow Ca(2+)-activated K(+) current by 4-aminopyridine in rat hippocampal CA1 pyramidal neurones.

ABSTRACT

1. The effect of 4-aminopyridine (4-AP) on the slow afterhyperpolarization (sAHP) seen after high frequency dendritic or somatic firing was investigated in rat hippocampal CA1 pyramidal neurones (PC). Intracellular recordings were obtained from the distal apical dendrites and somata and suprathreshold depolarizing current pulses were used to evoke a sAHP. The sAHP was blocked by low concentrations of carbacholine (Cch) but insensitive to high concentrations of apamin. 2. In the presence of extracellular 4-AP, the first dendritic sAHP evoked was reduced compared to a maximal sAHP evoked in the absence of 4-AP. The reduction was evident at submillimolar concentration and increased to about 80% with 4 mM 4-AP. 3. The stability of the 4-AP-induced block was affected by the type of anion used in the electrode solution. With K(+) acetate (KAc) or K(+) methylsulphate (KMeSO(4)) containing electrodes, the block was progressively removed during the initial 300 - 400 s of recordings. With KCl containing electrodes, the block remained stable and was 10% larger than that obtained with acetate. Detailed investigations showed that intracellular acetate promotes the removal of the 4-AP-induced block in an activity-dependent manner. 4. Intracellularly applied 4-AP also induced an acetate-sensitive block of the dendritic sAHP. 5. 4-AP also blocked the somatic sAHP and the stability of the block showed the same sensitivity towards anions as the dendritic sAHP. 6. Thus 4-AP appears to block the slow Ca(2+)-activated K(+) current underlying the sAHP in a complex manner which is sensitive to certain types of anions.