Voltage- and ligand-activated inwardly rectifying currents in dorsal raphe neurons in vitro

Intracellular recordings were made from neurons in rat dorsal raphe in the slice preparation maintained at 37°C. The single-electrode voltage-clamp method was used to measure membrane currents at potentials more negative than rest (-60 mV). Three types of inward rectification were observed: 2 in the absence of any drugs and the third induced by 5-HT1 and GABA-B receptor agonists. In the absence of any drugs, an inward current activated over 1-2 sec when the membrane potential was stepped to potentials more negative than -70 mV. This current was blocked by cesium (2 mM) and resembles I(Q) or I(H). A second inward current (I(IR)) occurred at membrane potentials near the potassium equilibrium potential (E(K)). This inward current activated within the settling time of the clamp and was abolished by both barium (10-100 μM) and cesium (2 mM). 5-HT1 agonists activated a potassium conductance that hyperpolarized the cells at rest. This potassium conductance was about 2 nS at -60 mV and increased linearly with membrane hyperpolarization to about 4 nS at -120 mV. Baclofen activated a potassium conductance identical in amplitude and voltage dependence to that induced by 5-HT1 agonists. Both the baclofen- and 5-HT-induced currents were nearly abolished in animals pretreated with pertussis toxin. The results indicate that a common potassium conductance is increased by 5-HT acting on 5-HT1 receptor and baclofen acting on GABA-B receptors. This potassium conductance rectifies inwardly and is distinct from the Q-current. The ligand-activated potassium conductance also differs from the other form of inward rectification (I(IR)) in its voltage dependence and sensitivity to pertussis toxin.