Chapter openers neurotransmitter

Box 1-1 describes the process by which neurotransmitters are released from a nerve cell in discrete bursts. The neurotransmitter measured by the electrode at the opening of this chapter is dopamine. Each dopamine molecule that diffuses to the electrode releases two electrons. The charge transferred to the electrode by burst 1 in panel c of the chapter opener is 0.27 pC (picocoulombs, 10 C). One coulomb of charge corresponds to 6.24 X lO electrons. How many molecules are released in burst 1 ... 

Other ion channels are closed at rest, but may be opened by a change in membrane potential, by intracellular messengers such as Ca + ions, or by neurotransmitters. These are responsible for the active signalling properties of nerve cells and are discussed below (see Hille 1992, for a comprehensive account). A large number of ion channels have now been cloned. This chapter concerns function, rather than structure, and hence does not systematically follow the structural classification. 

Opiates produce more discreet inhibitory effects since they bind to and activate inhibitory opioid receptors which, due to their restricted distribution, cause less widespread effects than those of the barbiturates and alcohol. Activation of the opioid receptors leads to a decrease in release of other neurotransmitters (glutamate, NA, DA, 5-HT, ACh, many peptides, etc.) and direct hyperpolarisation of cells by opening of K+ channels and decreasing Ca + channel activity via predominant actions on the mu opiate receptor (see Chapter 12). 

Muscle cell membranes of nematodes possess ion channel receptors that are opened by neurotransmitters and which are gated by selective therapeutic agents. This chapter is an introduction to the physiology and pharmacology of ligand-gated ion channels of nematode muscle. 

Figure 14.10 Diagrammatic representation of regulation of the opening of an ion channel by phosphoiylation of a protein in the channel. The neurotransmitter-receptor complex functions as a nucleotide exchange factor to activate a G-protein which then activates a protein kinase. This is identical to control of G-proteins in the action of hormones (Chapter 12, see Figure 12.21). Phosphorylation of a protein in the ion channel opens it to allow movement of Na+ ions. The formation of the complex, activation of the G-protein and the kinase takes place on the postsynaptic membrane. An example of the structural organisation and the involvement of a G-protein is shown in Chapter 12 (Figure 12.6).

Several classes of drugs, notably the antipsychotics, discussed in Chapter 34, interfere with dopaminergic transmission. In general, dopamine appears to be an inhibitory neurotransmitter. Five dopamine receptors have been identified the most important and best studied are the Dj. and D2.receptor groups. The Dj receptor, which increases cyclic adenosine monophosphate (cAMP) by activation of adenylyl cyclase, is located primarily in the region of the putamen, nucleus accum-bens, and in the olfactory tubercle. The D2 receptor decreases cAMP, blocks certain calcium channels, and opens certain potassium channels. 

As described in Chapter 4, regulatory G proteins act as an intermediate link between receptor activation and the intracellular effector mechanism that ultimately causes a change in cellular activity. In the case of opioid receptors, these G proteins interact with three primary cellular effectors calcium channels, potassium channels, and the adenyl cyclase enzyme.27 At the presynaptic terminal, stimulation of opioid receptors activates G proteins that in turn inhibit the opening of calcium channels on the nerve membrane.65 Decreased calcium entry into the presynaptic terminal causes decreased neurotransmitter release because calcium influx mediates transmitter release at a chemical synapse. At the postsynaptic neuron, opioid receptors are linked via G proteins to potassium channels, and... 

As the reader can appreciate, extremely low concentrations of metal ions are able to orchestrate a multitude of activities in the brain, controlling the opening of various ion channels as well as activating various neurotransmitter receptors. Clearly, changes in the concentrations of such metal ions will induce adverse effects and induce the demise of neurons and other cell types. This will be considered in the next chapter. 

Release of the neurotransmitter dopamine from a single active zone on a cell surface can be monitored by placing a nanoelectrode next to the cell, as shown at the opening of this chapter. When stimulated by ion injected near the cell, vesicles release dopamine by exocytosis. Each dopamine molecule that diffuses to the nanoelectrode gives up two electrons. Panel c at the beginning of the chapter shows four pulses measured over a period of 1 minute near one active zone. Each pulse lasts 10 milliseconds and has a peak current of — 10-50 picoamperes. The number of electrons in a pulse tells us how many dopamine molecules were released from one vesicle. 

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