Epilepsie-Tagebuch

Nav1.7 Sodium Channel Isoform is Expressed in Growth Cones of Hippocampal Neurons in Culture

Abstract

Valeria Bonetti, Jeismar Carballo, Lisbeth Garcia, Elizabeth Gómez and Marines Longart

Voltage Dependent Sodium Channels (VDSC) is fundamental for neuronal excitability and action potential propagation. There is a differential expression of the VDSC isoforms in different regions within the Central (CNS) and Peripheral Nervous System (PNS). The different isoforms (Nav1.1–Nav1.9) are widely expressed within the nervous system during specific developmental stages; however, the precise subcellular distribution for some isoforms is still incomplete. VDSC are important therapeutic targets for a wide variety of pathophysiological conditions, including chronic pain, cardiac arrhythmia, and epilepsy. Studies on the genetic basis underlying several striking human phenotypes have revealed the importance of NaV1.7 in pain signalling pathways and as a therapeutic target for treatment of chronic pain. Given that NaV1.7 expression in CNS has not been precisely addressed, and that the determination of its precise location is important to understand its function within neurons, we attempted to study the NaV1.7 subcellular localization in hippocampal neurons in culture by immunofluorescence. On the other hand, we studied the NaV1.2 subcellular localization and compared its expression pattern with NaV1.7. NaV1.2 is a Tetrodotoxin (TTX)-sensitive channel, predominantly expressed in the central nervous system and its subcellular distribution has been widely studied in central neurons. When we compared NaV1.2 and NaV1.7 we observed a distinctive subcellular localization for these two isoforms. Additionally, using a PanNaV antibody, which recognizes all sodium channel isoforms, we observed that PanNaV signal overlapped NaV1.2 and NaV1.7 specific signals. PanNaV labeled the Axon Initial Segment (AIS), cell bodies and neurites. NaV1.2 specific signal was mainly observed in the AIS, soma, dendrites and Golgi apparatus; while NaV1.7 mainly was present in soma, axons and growth cones. Our findings describing Nav1.7 in growth cones represent a new subcellular localization for this isoform and provide new evidences that suggest additional roles in neuronal functioning within the CNS.