TASK-3, two-pore potassium channels, contribute to circadian rhythms in the electrical properties of the suprachiasmatic nucleus and play a role in driving stable behavioural photic entrainment

Abstract

ABSTRACT Stable and entrainable physiological circadian rhythms are crucial for overall health and well-being. The suprachiasmatic nucleus (SCN), the primary circadian pacemaker in mammals, consists of diverse neuron types that collectively generate a circadian profile of electrical activity. However, the mechanisms underlying the regulation of endogenous neuronal excitability in the SCN remain unclear. Two-pore domain potassium channels (K2P), including TASK-3, are known to play a significant role in maintaining SCN diurnal homeostasis by inhibiting neuronal activity at night. In this study, we investigated the role of TASK-3 in SCN circadian neuronal regulation and behavioural photoentrainment using a TASK-3 global knockout mouse model. Our findings demonstrate the importance of TASK-3 in maintaining SCN hyperpolarization during the night and establishing SCN sensitivity to glutamate. Specifically, we observed that TASK-3 knockout mice lacked diurnal variation in resting membrane potential and exhibited altered glutamate sensitivity both in vivo and in vitro. Interestingly, despite these changes, the mice lacking TASK-3 were still able to maintain relatively normal circadian behaviour.