The Na⁺/K⁺-ATPase Inhibitor Ouabain Has Different Effects on the Electrophysiological Properties of Excitatory and Inhibitory Neurons in the Entorhinal Cortex E

Abstract

Na+/K+-ATPase maintains the neuron’s resting potential and the transmembrane gradient of K+ and Na+ cations, thus regulating ion transport and cellular volume. Mutations in Na+/K+-ATPase genes that impair its function can cause significant impairments in the nervous system function, including the development of epilepsy, if not lethal. Different forms of Na+/K+-ATPase are expressed in various classes of neurons and exhibit different characteristics. Thus, the impaired function of Na+/K+-ATPase may differentially affect the functioning of inhibitory and excitatory neurons. This study aims to determine the effects of the Na+/K+-ATPase antagonist ouabain on the electrophysiological characteristics of pyramidal cells and fast-spiking interneurons, as well as its impact on synaptic transmission. The results indicate that exposure to 5 µM ouabain results in depolarization of the resting membrane potential by 5 mV, as well as decreased amplitude and increased duration of the action potential of pyramidal neurons. Furthermore, ouabain caused a decrease in the amplitude of afterhyperpolarization in fast-spiking i-nterneurons. Moreover, both types of neurons exhibited a decrease in the threshold of action potential generation and the current at which depolarization block occurs. The addition of ouabain did not alter other electrophysiological characteristics of neurons. Furthermore, ouabain rapidly attenuates GABAergic transmission without affecting e-xcitatory synaptic transmission. These new findings on the effects of ouabain on excitatory pyramidal neurons and inhibitory interneurons contribute to the understanding of the mechanism underlying changes in the balance of excitation and inhibition in neural networks under Na+/K+-ATPase function impairment.