Selective ligands for Na + /K + -ATPase α isoforms differentially and cooperatively regulate excitability of pyramidal neurons in distinct brain regions

What is it about?

The Sodium-potassium ATPase (NaKA) and its endogenous ligands the cardiotonic steroids (CTS), regulate neuronal excitability and are involved in modifying brain functioning. As such, alterations of NaKA and CTS were implicated in several neuropsychiatric disorders. Though all this information is well accepted, the effect of CTS on neuronal physiology throughout the brain and the differential physiological effects of the various isoforms of these molecules were not thoroughly studied. This study, using pharmacology and electrophysiology, addresses the fundamental question of how CTS manipulate NaKA activity in different regions of the mouse brain. Foremost, we demonstrate that NaKA's inhibition differentially alters neuronal properties and synaptic responses in distinct brain areas. In addition, we demonstrated a synergistic effect between the two types of CTS.

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Why is it important?

The Sodium-potassium ATPase (NaKA) and its endogenous ligands the cardiotonic steroids (CTS), regulate neuronal excitability and are involved in modifying brain functioning. As such, alterations of NaKA and CTS were implicated in several neuropsychiatric disorders. Though all this information is well accepted, the effect of CTS on neuronal physiology throughout the brain and the differential physiological effects of the various isoforms of these molecules were not thoroughly studied. This study, using pharmacology and electrophysiology, addresses the fundamental question of how CTS manipulate NaKA activity in different regions of the mouse brain. Foremost, we demonstrate that NaKA's inhibition differentially alters neuronal properties and synaptic responses in distinct brain areas. In addition, we demonstrated a synergistic effect between the two types of CTS.