Novel clustering of sodium channel Nav1.1 with ankyrin-G and neurofascin at discrete sites in the inner plexiform layer of the retina

Voltage-gated sodium channels cluster at sites of action potential generation and propagation by interacting with partner proteins such as neurofascin, an adhesion molecule in the L1 family, and ankyrin-G, a spectrin-binding protein required for sodium channel accumulation at axon initial segments. Here, we describe in the inner plexiform layer of the retina a novel site of high-density sodium channel clustering, marked by ankyrin-G and neurofascin. The sodium channel isoform at this site is Nav1.1, instead of the Nav1.6 channels more commonly found in association with the clustering machinery. During development, Nav1.2 channels first associate with ankyrin-G in the inner plexiform layer but are later replaced by Nav1.1, similar to the switch from Nav1.2 to Nav1.6 at nodes of Ranvier and initial segments. This represents the first instance of high-density clustering of Nav1.1 channels, which may contribute to synaptic interactions among retinal neurons in the inner plexiform layer.