Action potentials features

Lidocaine and mexiletine both suppress the action potential features induced by a-toxins (Khodorova et al 2001). At 5—20 /iM, L accelerates the decay of the plateau (Fig. 2), reduces its area by > 80%, and halves the amplitudes of the high-frequency, post-spike oscillatory activity (Fig. 3). By comparison, inhibition of directly stimulated propagating spikes in peripheral fibres requires 200-800 fiM L (Huang et al 1997). 

To achieve their different effects NTs are not only released from different neurons to act on different receptors but their biochemistry is different. While the mechanism of their release may be similar (Chapter 4) their turnover varies. Most NTs are synthesised from precursors in the axon terminals, stored in vesicles and released by arriving action potentials. Some are subsequently broken down extracellularly, e.g. acetylcholine by cholinesterase, but many, like the amino acids, are taken back into the nerve where they are incorporated into biochemical pathways that may modify their structure initially but ultimately ensure a maintained NT level. Such processes are ideally suited to the fast transmission effected by the amino acids and acetylcholine in some cases (nicotinic), and complements the anatomical features of their neurons and the recepter mechanisms they activate. Further, to ensure the maintenance of function in vital pathways, glutamate and GABA are stored in very high concentrations (10 pmol/mg) just as ACh is at the neuromuscular junction. 

Table 4.1 Distinguishing Features of Graded Potentials and Action Potentials Graded potentials Action potentials...

To achieve a strict time control of principal cells, GABAergic interneurons display several remarkable features. (1) Their action potential is traditionally faster than that of pyramidal cells and the kinetics of synaptic events that excite inhibitory cells are faster than those that excite pyramidal cells (Martina et al. 1998 Geiger et al. 1997). (2) The GABAergic interneurons are morphologically highly diverse, which reflects their multiple functions in neuronal networks... 

The worker heart muscle cells (as opposed to the cells in the conduction system, which are also specialized muscle cells) are peculiar in using both Na and Ca in the depolarization phase of the action potential (Figure 5.8b, bottom). While they do not normally create action potentials themselves, under pathological conditions some of them may show spontaneous discharge. This depolarization may then spread across the entire heart (or parts of it) and interfere with normal and regular activity. While both calcium and sodium channel blockers have their applications in treating heart arrhythmias, the beauty of the sodium channel blockers is that they will not interfere with the activity of the regular pacemakers (since those essentially don t use sodium channels). Another beneficial feature was pointed out above Lidocaine extends the duration of the inacti-... 

The exocytosis of neurotransmitters from synaptic vesicles Involves targeting and fusion events similar to those that lead to release of secreted proteins In the secretory pathway. However, several unique features permit the very rapid release of neurotransmitters In response to arrival of an action potential at the presynaptic axon terminal. For example. In resting neurons some neurotransmitter-fllled synaptic vesicles are docked at the plasma membrane others are In reserve In the active zone near the plasma membrane at the synaptic cleft. In addition, the membrane of synaptic vesicles contains a specialized Ca -blndlng protein that senses the rise In cytosolic Ca " after arrival of an action potential, triggering rapid fusion of docked vesicles with the presynaptic membrane. 

The mechanism of action of local anesthetics can be understood primarily on the basis of nerve fiber electrophysiology and physicochemical features of the drugs. In brief, they raise the electric threshold for stimulation, which in turn slows down the rate at which an impulse travels down the nerve fiber. The process by which nerve conduction occurs (Fig. 8-3, and discussion thereof) is essentially impeded. The stabilization of the neuronal membrane does not allow for the depolarization when the action potential reaches the area of blockade. 

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