title: Extracellular sodium modulates the excitability of cultured hippocampal pyramidal cells.
abstract: Recent studies demonstrated a photophobia mechanism with modulation of nociceptive, cortico-thalamic neurons by retinal ganglion cell projections; however, little is known about how their neuronal homeostasis is disrupted. Since we have found that lumbar cerebrospinal fluid (CSF) sodium increases during migraine and that cranial sodium increases in a rat migraine model, the purpose of this study was to examine the effects of extracellular sodium ([Na(+)](o)) on the intrinsic excitability of hippocampal pyramidal neurons. We monitored excitability by whole cell patch using a multiplex micropipette with a common outlet to change artificial CSF (ACSF) [Na(+)](o) at cultured neurons accurately (SD<7 mM) and rapidly (<5s) as determined by a sodium-selective micro-electrode of the same size and at the same location as a neuronal soma. Changing [Na(+)](o) in ACSF from 100 to 160 mM, choline-balanced at 310-320 mOsm, increased the action potential (AP) amplitude, decreased AP width, and augmented firing rate by 28%. These effects were reversed on returning the ACSF [Na(+)](o) to 100mM. Testing up to 180 mM [Na(+)](o) required ACSF with higher osmolarity (345-355 mOsm), at which the firing rate increased by 36% between 100 and 180 mM [Na(+)](o), with higher amplitude and narrower APs. In voltage clamp mode, the sodium and potassium currents increased significantly at higher [Na(+)](o). These results demonstrate that fluctuations in [Na(+)](o) modulate neuronal excitability by a sodium current mechanism and that excessively altered neuronal excitability may contribute to hypersensitivity symptoms.
authors.affiliation: Molecular Neurology Program, Huntington Medical Research Institutes, 99 North El Molino Avenue, Pasadena, CA 91101, USA.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Arakaki
authors.forename: Hailey
authors.initials: H
authors.lastname: Foster
authors.forename: Lei
authors.initials: L
authors.lastname: Su
authors.forename: Huy
authors.initials: H
authors.lastname: Do
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wain
authors.forename: Alfred N
authors.initials: AN
authors.lastname: Fonteh
authors.forename: Feimeng
authors.initials: F
authors.lastname: Zhou
authors.forename: Michael G
authors.initials: MG
authors.lastname: Harrington
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D045604:Extracellular Fluid / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000502:physiology*
chemical_list: D012964:Sodium