Scientists at Yale School of Medicine and Veterans Affairs Connecticut Healthcare System show at single-molecule resolution how nerve cells build their electrically excitable membranes.
Electrical excitability is a fundamental feature of nerve cells, also called neurons. It enables neurons to code and transmit information in the form of electrical impulses to and from the brain. Sodium channels are key players in the generation of electrical impulses and work like molecular batteries within neuronal cell membranes.
The Yale-VA team utilized high-resolution microscopy of fluorescence tagged sodium channels to observe, in real time, the building of cell membranes of sensory neurons that regulate pain sensation. The convergence of cutting edge imaging and molecular technologies has made it possible to track the distribution, dynamics, and long-distance transport of sodium channels for the first time in sensory neurons.
“For a neuron whose cell body is approximately 0.1 millimeter in diameter, transport and on-demand delivery of sodium channels to distances up to a meter or more, is a remarkable feat,” notes Elizabeth Akin, first author on the paper, and postdoctoral scientist in the department of neurology at Yale. “This work provides a window into the process by which sensory neurons regulate their membrane excitability through distribution of sodium channels under conditions that reflect development and disease.”
The findings of the study appear in the October 23, 2019 issue of Science Advances.
"There are several very exciting aspects to this work. First, it shows at a fundamental level how nerve cells build their membranes. In a sense, we are learning how the building blocks that make impulses in nerve cells are assembled. Second, this work shows us how inflammation can perturb that process. That is a very important step in understanding how inflammation causes pain,” notes co-senior author Stephen Waxman, the Bridget Marie Flaherty professor of neurology and professor of neurobiology and of pharmacology at Yale, and director of rehabilitation research at VA Connecticut.
Other Yale authors on the paper are Grant P. Higerd, Malgorzata A. Mis, Brian S. Tanaka, Talia Adi, Shujun Liu, Fadia B. Dib-Hajj, and Sulayman D. Dib-Hajj. The research was funded in part by the VA Rehabilitation Research Service and Medical Research Service, and the Paralyzed Veterans of America.