Neuroprotection--rationale for pharmacological modulation of Na(+)-channels.
The primary factor detrimental to neurons in neurological disorders associated with deficient oxygen supply or mitochondrial dysfunction is insufficient ATP production relative to their requirement. As a large part of the energy consumed by brain cells is used for maintenance of the Na+ gradient across the cellular membrane, reduction of energy demand by down-modulation of voltage-gated Na(+)-channels is a rational strategy for neuroprotection. In addition, preservation of the inward Na+ gradient may be beneficial because it is an essential driving force for vital ion exchanges and transport mechanisms such as Ca2+ homeostasis and neurotransmitter uptake.
Urenjak
J
J
Pfizer Central Research, Sandwich, United Kingdom.
Obrenovitch
T P
TP
D000818:Animals; D015536:Down-Regulation; D004734:Energy Metabolism; D006706:Homeostasis; D015640:Ion Channel Gating; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism
D018696:Neuroprotective Agents; D015222:Sodium Channels; D012964:Sodium