TASK-3 two-pore domain potassium channels enable sustained high-frequency firing in cerebellar granule neurons

The ability of neurons, such as cerebellar granule neurons ( CGNs), to fire action potentials ( APs) at high frequencies during sustained depolarization is usually explained in relation to the functional properties of voltage-gated ion channels. Two-pore domain potassium ( K-2P) channels are considered to simply hyperpolarize the resting membrane potential ( RMP) by increasing the potassium permeability of the membrane. However, we find that CGNs lacking the TASK-3 type K2P channel exhibit marked accommodation of action potential firing. The accommodation phenotype was not associated with any change in the functional properties of the underlying voltage-gated sodium channels, nor could it be explained by the more depolarized RMP that resulted from TASK-3 channel deletion. A functional rescue, involving the introduction of a nonlinear leak conductance with a dynamic current clamp, was able to restore wild-type firing properties to adult TASK-3 knock-out CGNs. Thus, in addition to the accepted role of TASK-3 channels in limiting neuronal excitability, by increasing the resting potassium conductance TASK-3 channels also increase excitability by supporting high-frequency firing once AP threshold is reached.