Nmda receptor-operated channel pathway free
The role of NMDA receptoroperated calcium channels in persistent nociception after formalininduced tissue injury pretreatment with the calcium ionophore A or the calcium channel agonist
At resting potential, the pore of the NMDA receptor channel is blocked by magnesium ions. Upon depolarization, the magnesium ions are removed from the pore, and the channel can pass current. potentiation (LTP), and the weakening of synapses, through longterm depression (LTD).
Physiology and pathology of NMDA receptors. A schematic representation of the sites at which NMDA receptor channel activity can be modified. Pathways to neuronal injury and apoptosis. in
MK80 1 is a noncompetitive NMDA antagonist that blocks the influx of calcium through NMDA receptoroperated calcium chan nels; CNQX is a selective antagonist of AMPAkainate receptors.
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On the other hand, inactivation of ERK (by extrasynaptic NMDA receptor stimulation) is associated with calpain activation and STEP cleavage [. Ca 2 influx through extrasynaptic NMDARs involves binding of the phosphatase STEP to the channel, with direct inhibition of ERK 12. Another key player, CaMKII, appears to have a role in the activation of both pathways (synaptic and extrasynaptic
channel blockers and NMDA receptors would clearly advance the prospects of designing new NMDA antagonists for therapeutic use. The classical description of open channel block, based on block of nicotinic acetylcholine receptors by local anesthetics, utilized the sequential model (Adams, 1976; Neher and Steinbach, 1978).
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