KV7/M channels mediate osmotic modulation of intrinsic neuronal excitability.
Modest decreases in extracellular osmolarity induce brain hyperexcitability that may culminate in epileptic seizures. At the cellular level, moderate hyposmolarity markedly potentiates the intrinsic neuronal excitability of principal cortical neurons without significantly affecting their volume. The most conspicuous cellular effect of hyposmolarity is converting regular firing neurons to burst-firing mode. This effect is underlain by hyposmotic facilitation of the spike afterdepolarization (ADP), but its ionic mechanism is unknown. Because blockers of K(V)7 (KCNQ) channels underlying neuronal M-type K(+) currents (K(V)7/M channels) also cause spike ADP facilitation and bursting, we hypothesized that lowering osmolarity inhibits these channels. Using current- and voltage-clamp recordings in CA1 pyramidal cells in situ, we have confirmed this hypothesis. Furthermore, we show that hyposmotic inhibition of K(V)7/M channels is mediated by an increase in intracellular Ca(2+) concentration via release from internal stores but not via influx of extracellular Ca(2+). Finally, we show that interfering with internal Ca(2+)-mediated inhibition of K(V)7/M channels entirely protects against hyposmotic ADP facilitation and bursting, indicating the exclusivity of this novel mechanism in producing intrinsic neuronal hyperexcitability in hyposmotic conditions.
Caspi
Anna
A
Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah School of Medicine, Jerusalem 91120, Israel.
Benninger
Felix
F
Yaari
Yoel
Y
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D015640:Ion Channel Gating / Q000502:physiology; D051656:KCNQ Potassium Channels / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D009995:Osmosis / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000378:metabolism; D051381:Rats
D051656:KCNQ Potassium Channels