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

Abstract

AbstractSodium and potassium channels that regulate axonal spike propagation are highly organized at nodes of Ranvier by a spectrin-actin membrane periodic skeleton. STORM-TIRF microscopy was used to define the spatial organization over the soma of a complex of Cav1.3 calcium, RyR2, and IK potassium channels (CaRyK complex) that generate a slow AHP in hippocampal neurons. Nearest neighbor distance and non-negative matrix factorization analyses identified two spatial patterns as linear rows of 3-8 immuno-labeled clusters with 155 nm periodicity that extended to branchpoints, or as isolated clusters with 600-800 nm separation. The rows and isolated clusters for each of the CaRyK complex proteins closely overlapped with the patterns for spectrin βII and the actin linking proteins actinin I and II. Together the data reveal a close correspondence between the placement of CaRyK complex proteins and that of a net-like organization of spectrin βII across the soma. The regularity in the pattern of expression of these proteins at ER-PM junctions suggest their role as functional nodes of calcium- and calcium-gated potassium channels to control the pattern of spike output at the soma.