Tolbutamide suppresses slow and medium afterhyperpolarization in hippocampal slices.

Afterhyperpolarizations (AHPs) were recorded (in whole-cell mode, with KMeSO4-containing electrodes) after multiple spikes evoked with 200 ms current pulses. Bath applications of tolbutamide (0.5-1 mM) to 12 CA1 neurones nearly abolished the medium and slow component of AHPs. Thus the AHPs generated by 7-8 spikes (mostly) were reduced by 82.6 +/- 5.2% (s.e.m.) at the initial peak (mAHP) and by 85.0 +/- 5.8% 1 s later (sAHP). Glibenclamide (10 microM) had no comparable blocking effect. The previous finding that tolbutamide (but not glibenclamide) selectively suppresses the anoxic hyperpolarization of CA1 neurones is therefore consistent with the idea that the anoxic hyperpolarization is mediated by Ca-dependent (especially AHP-type) K channels.