Autism-Linked Variations in Ion Channel Genes Increase Brain Excitability
Neuronal communication guides virtually all aspects of brain development. To better understand Autism Spectrum Disorders (ASD), scientists are searching for autism-linked genes that regulate neuronal activity. Some of these genes encode ion channels, whose activation determines whether a neuron will fire a signal. Variations in ion channels influence neuronal survival, differentiation, migration, outgrowth, and synapse formation.
Ion channels are critical for shaping neuronal excitability. Neurons encode information using electrical signals derived from ion channels. At rest, each neuron has a negative charge. When a neuron receives signals from other neurons via synapses, ion channels open and the neuronal charge becomes either more positive or negative, depending on the type of ion. Once the charge of a neuron rises to a certain threshold, the neuron “fires” a signal to other neurons in a process called emitting an “action potential.”
Think of this process like the boiling of a teapot. The bottom of the teapot receives heat from the burners of the stove, much like how dendrites of a neuron receive synaptic signals. This heat boils the water in the teapot, converting it into steam, just as neurons convert synaptic signals into electrical charges. As the pressure builds, steam escapes through the spout, letting off a loud whistle. Likewise, once a neuron builds up enough positive charge, it sends a fast action potential down its axon to the next neuron.
Positive ion channels boost neuronal excitability by creating a more positive charge. However, the balance of neuronal excitability is crucial. Too much excitation leads to seizures and epilepsy, whereas too little prevents circuits from firing. Individuals with autism frequently also have epilepsy, suggesting that their brains are overexcited.
ASD-linked mutations in genes for calcium (Ca2+), sodium (Na+), and potassium (K+) ion channels enhance brain excitability, although the exact mechanisms are not well understood. Known ASD-associated mutations occur in the genes CACNA1C, CACNA1F, CACNA1G, and CACNA1H, which encode the L-type calcium channels Cav1.2 and Cav1.4 and the T-type calcium channels Cav3.1 and Cav3.2, respectively; the sodium channel genes SCN1A and SCN2A, which encode the channels Nav1.1 and Nav1.2, respectively; and the potassium channel genes KCNMA1 and KCNJ10, which encode the channels BKCa and Kir4.1, respectively.
Variations in ion channel genes are likely to affect a myriad of brain functions. Ion channels may even provide a link between genetics and the environment because environmental factors like mercury increase calcium signaling. The broad role of ion channels may help explain why ASD is so often accompanied by other neurological complications like sleep problems and epilepsy.
Catherine Croft Swanwick, Ph.D.
Originally written June 23, 2010 Last updated September 29, 2011 by Catherine Croft Swanwick, Ph.D.