Somatostatin sharpens the neuronal action potential by increasing K ⁺ and decreasing Ca ²⁺ conductances

Somatostatin (SST) is a neuropeptide whose biological function has initially been described in the hypothalamus. However, SST-expressing neurons are also found in the neocortex or hippocampus, and the majority of these neurons are GABAergic interneurons (INs), so called SST-INs. Numerous studies on non-cortical cells suggest that SST acts via different K + channels to dampen cell excitability, however questions remain as to the exact mechanisms whereby SST mediates these effects on cortical pyramidal cells (PCs). The present study analysed the capacity of SST to inhibit action potential (AP) firing in layer II/III PCs of the anterior cingulate cortex (aCC). It is reported here that SST decreases PC excitability mainly via G protein-coupled inwardly rectifying potassium (GIRK) and Kv 7 channels. Furthermore, activation of GIRK and Kv 7 channels together with inhibition of voltage-gated Ca 2+ channels (VGCCs) is responsible for SST-dependent inhibition of AP firing and increase in the afterhyperpolarisation (AHP) amplitude following a spike. By analysing single spike kinetics before and after SST exposure, this study further identifies Ca 2+ activated K + (K Ca ) channels as target molecules of SST receptor activation. In summary, the present study promotes our current understanding of the ionic mechanisms that lead to a SST-dependent loss in excitability.