Complementary functions of SK and Kv7/M potassium channels in excitability control and synaptic integration in rat hippocampal dentate granule cells
Published online on February 14, 2014
Abstract
Key points
Previous studies showed that different firing patterns of hippocampal dentate granule cells (DGCs) can trigger different network responses. However, the intrinsic DGC mechanisms controlling their excitability, spike patterns and synaptic integration in DGCs, remain poorly understood.
SK and Kv7/M channels play important roles controlling neuronal integration and excitability, but their specific roles vary between cell types. Both channel types are expressed in DGCs, but their roles are unclear.
We found that SK channels are the main generators of medium afterhyperpolarizations in DGCs, thus causing negative feedback regulation of spiking (spike frequency adaptation) and calcium influx.
In contrast, Kv7/M perform subthreshold and ‘feed‐forward’ control of input resistance, postsynaptic integration, action potential threshold and excitability, thus weakening EPSP–spike coupling.
Thus, in DGCs, the SK and Kv7/M channels seem to perform complementary functions in postsynaptic integration and excitability control. This may have important consequences for dentate network physiology.
Abstract
The dentate granule cells (DGCs) form the most numerous neuron population of the hippocampal memory system, and its gateway for cortical input. Yet, we have only limited knowledge of the intrinsic membrane properties that shape their responses. Since SK and Kv7/M potassium channels are key mechanisms of neuronal spiking and excitability control, afterhyperpolarizations (AHPs) and synaptic integration, we studied their functions in DGCs. The specific SK channel blockers apamin or scyllatoxin increased spike frequency (excitability), reduced early spike frequency adaptation, fully blocked the medium‐duration AHP (mAHP) after a single spike or spike train, and increased postsynaptic EPSP summation after spiking, but had no effect on input resistance (Rinput) or spike threshold. In contrast, blockade of Kv7/M channels by XE991 increased Rinput, lowered the spike threshold, and increased excitability, postsynaptic EPSP summation, and EPSP–spike coupling, but only slightly reduced mAHP after spike trains (and not after single spikes). The SK and Kv7/M channel openers 1‐EBIO and retigabine, respectively, had effects opposite to the blockers. Computational modelling reproduced many of these effects. We conclude that SK and Kv7/M channels have complementary roles in DGCs. These mechanisms may be important for the dentate network function, as CA3 neurons can be activated or inhibition recruited depending on DGC firing rate.