Synapse action

The axon is a long narrow process that extends from the cell body and conveys action potentials toward the neuron s synapses. Action poten-... 

Thus nicotinoids that have the highest insecticidal action have the highest piC and, consequently, exist largely in the ionized form at physiological pH. This produces the anomaly that the compounds that are most highly ionized react most rapidly with the receptor protein, yet they are less able to penetrate through the ionic barrier surrounding the insect nerve synapse. 

Selected for clinical trials as a compound to calm agitated patients, imipramine was relatively ineffective. However, it was observed to be effective in the treatment of certain depressed patients (38). Early studies on the mechanism of action showed that imipramine potentiates the effects of the catecholamines, primarily norepinephrine. This finding, along with other evidence, led to the hypothesis that the compound exerts its antidepressant effects by elevating norepinephrine levels at central adrenergic synapses. Subsequent studies have shown that the compound is a potent inhibitor of norepinephrine reuptake and, to a lesser extent, the uptake of serotonin, thus fitting the hypothesis that had been developed to explain the antidepressant actions ofMAOIs. 

Long nerve-cell process transmitting the action potential and ending as the synapse. 

ChEs control the duration of ACh-mediated action on post-synaptic receptors in cholinergic synapses, and have non-hydrolytic roles in nervous systems development and plasticity. 

Neuromuscular junction (NMJ) is the synapse or junction of the axon terminal of motoneurons with the highly excitable region of the muscle fibre s plasma membrane. Neuronal signals pass through the NMJ via the neurotransmitter ACh. Consequent initiation of action potentials across the muscle s cell surface ultimately causes the muscle contraction. 

Figure 1.6 Presynaptic inhibition of the form seen in the dorsal horn of the spinal cord, (a) The axon terminal (i) of a local neuron is shown making an axo-axonal contact with a primary afferent excitatory input (ii). (b) A schematic enlargement of the synapse, (c) Depolarisation of the afferent terminal (ii) at its normal resting potential by an arriving action potential leads to the optimal release of neurotransmitter, (d) When the afferent terminal (ii) is already partially depolarised by the neurotransmitter released onto it by (i) the arriving acting potential releases less transmitter and so the input is less effective...

Despite the above precautions, it is still possible that NT spillover and extrasynaptic action may occur and indeed could be required in some instances. Thus the diffusion of glutamate beyond the synapse could activate extrasynaptic high-affinity NMDA or metabotropic receptors (Chapter 9) to produce long-lasting effects to maintain activity in a network. This may be important in long-term potentiation and memory effects. Crosstalk between synapses could also act as a back-up to ensure that a pathway functions properly (see Barbour and Hausser 1997). 

Figure 5.5 Diagrammatic representation of a synapse showing the sites at which drugs may act to increase or decrease the concentration and action of a neurotransmitter. Drugs can affect the synthesis (1), storage (2), release (3), action (4) and destruction (5) of the transmitter. The different ways in which they achieve this (a, b, c) are outlined in Table 5.1...

The sites of action of drugs affecting the dopamine synapse are indicated in Fig. 7.3. Those modifying the synthesis, storage, release, uptake and metabolism of DA have been covered above in the appropriate sections on neurochemistry. The actions and uses of agonists and antagonists are outlined in Table 7.4 and covered in detail in appropriate chapters. Their structures are given in Fig. 7.6. 

As with other monoamines, the actions of 5-HT are terminated by its reuptake from the synapse by another member of the family of Na+/CU-dependent transporters. The 5-HT transporter has many features in common with its catecholamine equivalent (described fully in Chapter 8 see Fig. 8.7), including its presumed 12 transmembrane-spanning domains. However, the cloned 5-HT transporter has a for 5-HT of about 450 nM whereas its K for both noradrenaline and dopamine is some ten thousand-fold greater (Povlock and Amara 1997) which means that it is relatively selective for uptake... 

Figure 10.2 Site of action of drugs affecting glutamate synapses...

---