Ion Channel Functions in Early Brain Development.

During prenatal brain development, ion channels are ubiquitous across several cell types, including progenitor cells and migrating neurons but their function has not been clear. In the past, ion channel dysfunction has been primarily studied in the context of postnatal, differentiated neurons that fire action potentials – notably ion channels mutated in the epilepsies – yet data now support a surprising role in prenatal human brain disorders as well. Modern gene discovery approaches have identified defective ion channels in individuals with cerebral cortex malformations, which reflect abnormalities in early-to-middle stages of embryonic development (prior to ubiquitous action potentials). These human genetics studies and recent in utero animal modeling work suggest that precise control of ionic flux (calcium, sodium, and potassium) contributes to in utero developmental processes such as neural proliferation, migration, and differentiation. Developmental channelopathy is an ion channel disease with a pathophysiological origin during the gestational period. Human genetics studies reveal that individuals with dysfunctional sodium and glutamate channels can have improperly folded cerebral cortices. The gestational brain is comprised of diverse and transient cell types, including dividing and newly differentiated cells. Some of the mechanisms involved in developmental channelopathies during gestation are different from those acting postnatally during ion channel diseases. Ion channel mutations that result in greater excitability (gain-of-function) are often associated with human cortical malformations. [ABSTRACT FROM AUTHOR]