An electro-mechanical mechanism of spike propagation in myelinated axons

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Nerve cells send electrical impulses down long fibers called axons. Many axons are surrounded with a layer of insulation called the myelin sheath, a structure that ensures that the impulses propagate very rapidly and reliably. Tiny gaps in the sheath, called nodes of Ranvier, serve to amplify the electrical impulses, driving them forward to the end of the axon, where chemical signals are sent to other neurons or muscle cells at structures called synapses. In multiple sclerosis (MS) and other demyelinating diseases the myelin sheath is damaged and the nodes of Ranvier are disrupted, slowing or even stopping the electrical impulses from reaching the synapse. Our aim is to test a new idea that could fundamentally change our understanding of how electrical impulses are amplified at nodes and how they travel so fast along axons. Instead of the amplification mechanism being purely electrical, we propose a new mechanism, in which physical swelling of the node along a novel molecule that senses swelling, are crucial for amplifying electrical impulses, causing them to propagate faster and more reliably. This idea was spawned by the recent discovery that a specialized mechanically-sensitive ion channel named TRAAK is highly concentrated at nodes. TRAAK is a potassium channel, which are already known to be important for shaping electrical impulses. The presence of TRAAK at nodes raises the possibility that it serves a key electro-mechanical function. This exploratory/developmental project will answer 3 key questions: 1) To what extent do electrical impulses cause swelling of nodes of Ranvier in the brain? 2) Are TRAAK channels necessary for proper electrical impulse propagation in myelinated axon in the brain? 3) Can optical manipulation of a genetically-engineered photo-controlled version of TRAAK restore proper spike propagation in myelinated axons in the brain? Results gleaned from this work will be of great importance for understanding fundamental physiological processes necessary for normal function of the nervous system. These findings will provide new insights into events that occur in demyelinating diseases such as MS, and may lead to new treatment strategies, including the development of drugs for mitigating their debilitating symptoms.