THEOPHYLLINE AFFECTS 3 DIFFERENT POTASSIUM CURRENTS IN DISSOCIATED RAT CORTICAL-NEURONS

1. The effects of theophylline in pyramidal neurones acutely dissociated from the rat frontal cortex were investigated in the whole-cell configuration, using the nystatin-perforated patch-clamp technique. 2. Ten millimolar theophylline evoked triphasic responses: a small slow outward current (L(so)), then a large transient outward current (I(to)) and finally a slow sustained inward current (I(si)). The reversal potentials of the three current components shifted 56-58 mV for a 10-fold change in extracellular K+ concentration, thereby indicating that all these current components were predominantly carried by K+. 3. I(so) had no voltage dependence, whereas I(to) showed a steep outward rectification. I(so) was relatively resistant to tetraethylammonium (TEA) with an IC50 of 10 mM. I(to)) was susceptible to submillimolar TEA with an IC50 of 0.8 mM. 4. I(si) was a net inward current mainly resulting from suppression of the M-current (I(M)). 5. These three current components had a distinct concentration dependence; in particular, I(si) was evoked at a relatively lower concentration range. 6. I(to) was not observed when the intracellular Ca2+ was chelated by 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) of 10 mM, using the conventional whole-cell recording configuration, whereas both I(so) and I(si) were retained but gradually diminished. 7. In Ca2+-free external solution, these responses were fully elicited by the first application of theophylline. However, I(to) disappeared during successive applications and I(so) but not I(si), also decreased. Similar results were obtained in the presence of ryanodine. 8. Theophylline apparently affects three different kinds of K+ currents in rat cortical neurones. Both I(so) and I(to) depend on internal calcium mobilized from an intracellular Ca2+ Store by theophylline, while I(si) was not primarily mediated by a change in [Ca2+]i.