REVERSIBLE INHIBITION OF I-K, I-AHP, I-H AND I-CA CURRENTS BY INTERNALLY APPLIED GLUCONATE IN RAT HIPPOCAMPAL PYRAMIDAL NEURONS

Previously, we reported that the spike frequency adaptation and slow a fterhyperpolarizations (sAHP) in hippocampal pyramidal neurones are be st preserved during whole-cell recording with a methylsulfate (MeSO(4) (-))- based internal solution, but undergo a fast rundown when glucona te- (Gluc(-))- based internal solution is used. Here we show, with int ernal perfusion of patch pipettes, the reversibility of the inhibitory effects of Gluc(-) on spike frequency adaptation and sAHP, and extend these observations to fast and medium-duration AHPs. Contrary to what might be expected based on Gluc(-) binding of Ca2+, the sAHP and its underlying current could be temporarily enhanced by adding 1-3 mM of t he calcium chelator BAPTA to the internal solution in the presence of Gluc(-). Replacement of internal MeSO(4)(-) with Gluc(-) did not affec t the membrane resting potential or the amplitude and duration of acti on potentials, but reversibly increased the cell input resistance and decreased the threshold current for spike generation. Gluc(-) reversib ly inhibited the hyperpolarization-activated non-selective cationic cu rrent (I-h), the depolarization-activated delayed rectifier K+ current (I-K), the high-voltage-activated Ca2+ current and the Ca2+-activated K+ current that underlies the sAHP. The combination of these effects of Gluc(-) significantly alters the electrophysiological ''fingerprint '' of the neurone.