Ion channels can multi-task

Ion channels produce action potentials by allowing specific ions to pass in or out of cells across its membrane by using specific ion channels. When action potentials begin, the concentration of calcium ions at the axon initial segment also increases. Until now it was unclear which ion channels were responsible for this entry of calcium.

Researchers from the Kole Group discovered that calcium ions enter the axon through voltage-gated natrium channels. They observed that specific natrium channel blockers prevent most calcium elevations inside the axon and the calcium influx behaves as if being a natrium ion. “Using slices of the brain and a fast camera to visualize fluorescent sensors for calcium, we imaged axons and observed hot spots where calcium increases that overlapped with natrium channel clusters, both in rat and human axons”, explains Naomi Hanemaaijer, PhD student at the NIN.

Double entry

Furthermore, when the researchers expressed the proteins that form the macromolecules for natrium channels in human embryonic kidney cells, calcium ions passed together with natrium ions across the membrane. Together with the findings from a wide range of biophysical experiments, the results provide evidence for double entry of calcium and natrium, implicating that natrium channels are simultaneously responsible for multiple processes.

Although the amount of calcium entering via a single natrium channel is small, since they are present with many of thousands at critical hot spots in axons, they form an important calcium source at these sites. The results warrant molecular investigations to unravel the mechanisms of the selectivity filter. Interestingly, in patients with autism spectrum disorders genetic mutations have been discovered that change the natrium channel selectivity filter to favor calcium entry.