Research Projects

How are sodium channels clustered at nodes of Ranvier?

Prior to myelination (and following demyelination) sodium channels are present throughout the axon membrane at low density. A former graduate student, Jin Wu, characterized these and other axonal channels with patch clamp measurements. When glial cells (Schwann cells in the peripheral nervous system) adhere to axons and begin myelination, sodium channels rapidly cluster adjacent to the tips of the glial processes that are extended during early stages of ensheathment.

Learn more about How are sodium channels clustered at nodes of Ranvier?

Ion channels are distributed at specific sites in neurons

Neurons are highly polarized cells, and their proper functioning depends on specific targeting of membrane proteins, including ion channels, to appropriate regions. For example, voltage-dependent sodium channels must be localized at high density at the initial segment of the axon, and must also be clustered at nodes of Ranvier. The initial segment is the site at which synaptic inputs are integrated and the action potential is initiated. The nodes of Ranvier are gaps in the insulating myelin, and constitute regions where the impulse is regenerated for propagation down the axon.

Learn more about Ion channels are distributed at specific sites in neurons

Neuronal polarity during development

Early in neuronal development, neurites become polarized into dendrites and the axon. One fundamental event involves the targeting of sodium channels to the initial segment of the axon, a site that may function as the zone of action potential initiation. In the figure above a motor neuron has been cultured from embryonic spinal cord. After 4 days in vitro the cell was labeled with antibodies against sodium channels (red) and MAP2, a somatodendritic marker (green). Only one neurite, destined to be the axon, has the cluster of sodium channels. In contrast with the situation at nodes of Ranvier, this channel clustering occurs independently of glial cells.

Learn more about Neuronal polarity during development

The role of voltage-dependent potassium channels in myelinated axons

Voltage-dependent potassium channels have a reciprocal relationship with sodium channels, and are located primarily in clusters several micrometers on either side of the node, as seen in the top figure. We have shown that axonal potassium channels play important roles during both early development and in disease. Over the first few postnatal days, Shaker-type potassium channels stabilize conduction and prevent repetitive firing. In disease, following demyelination the juxtaparanodal potassium channel clusters break up.

Learn more about The role of voltage-dependent potassium channels in myelinated axons