Forskolin mimics the dopamine-induced K+ conductance increase in identified neurons of Aplysia kurodai.

The ionic mechanism of the effect of micropressure ejection of dopamine (DA) and forskolin on the membranes of identified inhibition of long duration (ILD) neurons of Aplysia kurodai was investigated with conventional voltage-clamp and ion-substitution techniques. Ejection of DA and forskolin onto the neuropil of the ILD neuron produced a slow outward current (5-20 nA in amplitude; 10-60s in duration) associated with a conductance increase. The outward currents induced by DA and forskolin were consistently a linear function of the holding potential, reversing near the predicted potassium equilibrium potential (-80 mV), and were sensitive to changes in the concentration of extracellular K+ but not to extracellular Cl-. Bath-applied isobutylmethylxanthine (50 microM) prolonged the outward current induced by both DA and forskolin, but imidazole (5 mM) had an opposite effect on these currents. Tolbutamide (1-5 mM), a protein kinase inhibitor, reduced the current induced by both DA and forskolin. A antagonist for DA receptors in molluscan neuron, ergometrine maleate, (10 microM) completely abolished the outward current induced by DA, but the current induced by forskolin persisted in the presence of the DA-antagonist. Guanosine 5'O-(2-thiodiphosphate) (GDP beta S, 5-10 microM), an analogue of GDP inhibited the outward current induced by both DA and forskolin. These results suggest that dopamine acts on the ILD neurons of Aplysia kurodai by increasing K+ conductance. Forskolin can mimic the DA action, suggesting that the effect of dopamine is mediated by increased intracellular cAMP.