The serotonergic inhibitory postsynaptic potential in prepositus hypoglossi is mediated by two potassium currents

Synaptic inhibition mediated by the activation of potassium channels has been reported from several types of neurons. In each case, despite mediation by different neurotransmitters, the K⁺ conductance underlying the synaptic potential is activated by a G protein and inwardly rectifies. We report here a second K⁺ current that contributes to synaptic inhibition. Intracellular recordings were made from guinea pig nucleus prepositus hypoglossi in vitro, where we have described a 5-HT-mediated IPSP. Voltage-clamp analysis of the current induced by applied 5-HT revealed two separate conductances: an inwardly rectifying, rapidly activating K⁺ current (I(IR)) and an outwardly rectifying, slowly activating K⁺ current (I(OR)). I(IR) was blocked by extracellular Ba²⁺ (200 μM) and TEA⁺ (126 mM). I(OR) was insensitive to this concentration of Ba²⁺ and TEA⁺, but was inhibited by Cd²⁺ and intracellular BAPTA, indicating Ca dependence. Single focal electrical stimuli evoked a 5-HT-mediated IPSP, or under voltage clamp, an inhibitory postsynaptic current (IPSC). Ba²⁺ blocked only a component of this IPSC, which corresponded to the current caused by I(IR). When multiple stimuli were applied (to prolong the release of transmitter), the time-dependent current I(OR). was more fully activated, resulting in an augmentation of the IPSC. We conclude that the IPSC is caused by both currents and that its amplitude can be modulated by the degree to which I(OR) is activated. This represents a mechanism by which synaptic responses can be potentiated.