Ion channels that mediate calcium-dependent control of spike patterns are spatially organized across the soma in relation to a cytoskeletal assembly

A spectrin-actin Membrane Periodic Skeleton defines the distribution of ion channels that support spike conduction down axons, but it is not known how calcium and potassium channels are organized at the soma to control spike output patterns. The hippocampal pyramidal cell slow AHP is generated by a CaRyK protein complex of Cav1.3 calcium, RyR2, and IK potassium channels. Super resolution imaging and dimension reduction identified a highly organized distribution of CaRyK proteins across the spectrin cytoskeleton. Rows of CaRyK protein clusters with 150 nm periodicity extended to branchpoints to align with a non-rigid lattice-like structure of spectrin βII and the actin linking proteins actinin I and II. The slow AHP was highly dependent on the integrity of the spectrin cytoskeleton that colocalized CaRyK proteins. The data indicate that the somatic slow AHP is generated by CaRyK proteins distributed as functional ion channel nodes across a Spectrin Polygonal Lattice. Graphical Abstract