Appearance and Distribution of Voltage-Gated Sodium Channels in Excitable and Non-Excitable Cells of the Human Brain

Sodium currents were first discovered by Hodgkin and Huxley using the voltage clamp technique, as reported in their groundbreaking series of papers in 1952. The molecular characterization of sodium channels (Nav) in excitable cell membranes was subsequently conducted in the 1980s. Current knowledge highlights their pharmacological and electrophysiological diversity, as well as their unique tissue-specific expression patterns. Alterations in voltage-gated sodium channels and ionic imbalances within neural networks have been implicated in epilepsy. This study aims to investigate the appearance and distribution of voltage-gated sodium channels in the brains of epileptic patients.
The brain samples were obtained from the Netherlands Brain Bank, Netherlands Institute for Neuroscience,Amsterdam (open access: www.brainbank.nl). Immunoexpression of voltage-gated sodium channels in different regions of the human brain was detected using conventional immunohistochemistry.
The expression of Nav varied across the human brain regions studied. The expression of Nav1.1 and Nav1.7 was weak in all regions, including the hippocampus, cerebellum, and temporal lobe, whereas Nav1.2 expression was intense in the white matter, as well as in the granule layer and the lower part of the molecular layer of the cerebellum, and weak in the hippocampus. In the cerebellum, non-excitable cells, such as astrocytes and microglia, exhibited weak Nav1.1 expression.
Navs are expressed in excitable cells, such as neurons, as well as in non-excitable cells like astrocytes and macrophages. This diversity underlies a broad spectrum of effector functions, including cell excitability, ion homeostasis, and signaling.