IONOTROPIC AND METABOTROPIC ACTIVATION OF A NEURONAL CHLORIDE CHANNELBY SEROTONIN AND DOPAMINE IN THE LEECH HIRUDO-MEDICINALIS

1. Cl- channels on the pressure-sensitive (P) neuron in the leech are directly activated by synaptic release of serotonin (5-HT) and are ind irectly stimulated by the cAMP second messenger pathway, suggesting an unusual dual regulation of the channels. We have investigated the mod e of action of 5-HT and dopamine (DA) on a Cl- channel in adult P cell s in culture by recording from cell-attached patches. 2. 5-HT increase d Cl- channel activity only when included in the recording pipette and not when applied in the bath. 3. Pipette or, more effectively, bath a pplication of DA led to an increase in Cl- channel activity. This effe ct was blocked by the potent and specific dopaminergic (DA(1)) recepto r blocker, SCH-23390. 4. The stimulation by DA, but not by 5-HT, was a lso blocked by the cAMP-dependent protein kinase A (PKA) inhibitor Rp- cAMP and was mimicked by the membrane-permeant cAMP analogue dibutyryl cAMP (db-cAMP). 5. Our results show that 5-HT directly gates a Cl- ch annel that is also activated by DA via the cAMP pathway. This study de monstrates that a ligand-gated channel can be independently operated b y another transmitter acting via a second messenger pathway.