Dendritic Na+ channels

The dendrites of neurons adjacent to those which degenerate also show extensive growth and sprouting which could facilitate abnormal and disorganised synaptic transmission and cause hyperactivity. It is also known that the dendrites of cells around an alumina focus in monkeys, as well as in human epileptic brain, lose their spinous processes, which might contribute to the paroxysmal discharge by facilitating the spread of depolarisation to the neuron soma. Certainly an increase in the number of Na+ channels on the dendrites of spinal motoneurons, which would facilitate the occurrence of reactive dendritic Na+ spikes, has been seen after axotomy. 

Two effects relevant to the mechanism of action of lacosamide as an antiseizure drug have been described. Lacosamide enhances slow inactivation of voltage-gated Na+ channels. It also binds to the collapsin-response mediator protein, CRMP-2, thereby blocking the effect of neurotrophic factors such as BDNF and NT3 on axonal and dendritic growth. 

Several early studies using patch techniques have revealed voltage-dependent Na channels in the apical dendrites of pyramidal shaped cells from the mammalian CNS (Magee Johnston 1995, Spruston et al 1995, Stuart ... 

SCNSA is another major Na+ channel that is widely distributed in the CNS and PNS. SCNSA appears to be the only Na+ channel located in the nodes of Ranvier in adults, and is also found in cell bodies, dendrites, and presynaptic and postsynaptic membranes (Caldwell et al 2000, Schaller Caldwell 2000, Krzemien et al 2000). We have been studying four independent spontaneous... 

How does a neuron achieve its very long, branching structure Why does one part of a neuron become a dendrite and another an axon Why are certain key membrane proteins clustered at particular points—neurotransmltter receptors In postsynaptic densities in dendrites, Ca channels In axon termini, and Na" channels in myelinated neurons at the nodes of Ranvier Such questions of cell shape and... 

Electron microscopically (Fig. 3.5), the early lesion of the neuron is marked by dendritic swelhng (Auer et al., 1985). This spares the intervening neuropil. The lesion is the electron microscopic hallmark of an excitotoxin. The reason for this is the selective dendritic location of receptors. Thns, amino acids bind to glutamate excitatory receptors on neuronal dendrites, open Ca + and Na channels which lead also to water fluxes across the membrane, and to the swelling of dendrites, sparing the intervening axons. When cell membrane breaks spread to the soma or perikaryon, the neuron dies. 

Figure 2.4 Noradrenergic inhibition of Ca " currents and transmitter release in sympathetic neurons and their processes, (a) Inhibition of currents through N-type Ca " channels by external application of noradrenaline (NA) or by over-expression of G-protein P y2 subunits, recorded from the soma and dendrite of a dissociated rat superior cervical sympathetic neuron. Currents were evoked by two successive 10 ms steps from —70 mV to OmV, separated by a prepulse to -1-90 mV. Note that the transient inhibition produced by NA (mediated by the G-protein Go) and the tonic inhibition produced by the G-protein Piy2 subunits were temporarily reversed by the -1-90 mV depolarisation. (Adapted from Fig. 4 in Delmas, P et al. (2000) Nat. Neurosci. 3 670-678. Reproduced with permission), (b) Inhibition of noradrenaline release from neurites of rat superior cervical sympathetic neurons by the 2-adrenoceptor stimulant UK-14,304, recorded amperometrically. Note that pretreatment with Pertussis toxin (PTX), which prevents coupling of the adrenoceptor to Gq, abolished inhibition. (Adapted from Fig. 3 in Koh, D-S and Hille, B (1997) Proc. Natl. Acad. Sci. USA 1506-1511. Reproduced with permission)...

Receptors are located on non-motile cilia that project from the dendrite of the neurone into the mucus layer. It is the cilia that possess the receptor for the pheromone and respond to it via an effector system that results in opening of a Na" ion channel. This depolarises the membrane across the sensory cell which, if of sufficient magnitude, leads to generation of action potential along the axon with which it forms a synapse. The effector system is adenyl cyclase and the generation of cyclic AMP, a process that involves the G-protein (Figure 12.15). 

Nn Neuronal type, ganglion receptor CNS postganglionic cell body, dendrites Pentamer with and subunits only, eg, ( 4)2( 2)3 (CNS) or cx3 tx5(B2)3 (ganglia) Na +, K+ depolarizing ion channel... 

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