Nicotine Abuse

Tobacco consumption has been estimated to cause nearly 20 of deaths in developed countries, and smokers are more than 20 times more likely to develop lung cancer than individuals who do not smoke Peto et al, 1992 . Despite being aware of its harmful effects, most smokers find it extremely difficult to give up tobacco. Current evidence suggests that the addictive effects of tobacco are principally due to nicotine. It is likely that neuronal nAChRs are the principal target for the drug and that...

GABAa Receptors

The neurotransmitter y-aminobutyric acid GABA interacts with two major types of receptor the GABAa GABAaR and the GABAb receptors. GABAa receptors are anion-selective ligand-gated channels which mediate fast synap-tic inhibition in the CNS. They are widely distributed throughout the brain and spinal cord. Like the glycine receptors, the ligand-binding site and the anion channel form a single functional unit. Binding of GABA to its receptor opens an integral Cl channel, producing an increase in...

The y2 Knockout Mouse

Gaba Receptors

Mice in which the y2-subunit was 'knocked out' have provided insight into the importance of this subunit in the GABAA receptor complex Giinther et al., 1995 . These mice do not express the y2-subunit, but other types of GABAA subunits are expressed at similar levels to wild-type mice. They lack high-affinity benzodiazepine-binding sites in the brain and their behaviour is unaffected by diazepam, confirming that the y2-subunit forms an essential part of the benzodiazepine-binding site....

Myasthenia Gravis

Miniature End Plate Potentials

Myasthenia gravis is one of the best understood autoimmune diseases, with a prevalence in northern Europe of 7-9 cases per 100,000 people. Two-thirds of patients are women, in whom the disease often develops in early adult life, with a peak age of onset during the third decade both men and women can also develop the disease in later life. The hallmark of myasthenia gravis is a profound weakness of the skeletal muscle, which increases with exercise. It is caused by autoantibodies directed...

Aquaporin

Aquaporine Collecting Duct

The second water channel to be cloned, aquaporin 2 or AQP2, is 42 identical to AQP1 at the amino acid level Fushimi et al., 1993 . Human AQP2 is a 271 amino acid protein with a molecular mass of 29 kDa and a predicted transmembrane structure similar to that of AQP1 Sasaki et al., 1994 . The gene is located on chromosome 12q13 and contains four exons Table 19.1 . AQP2 is expressed exclusively in the collecting duct of the kidney and plays a fundamental role in the production of a concentrated...

Ion Channels Of The Vertebrate Immune System

FIGURE 23.1 MECHANISM OF COMPLEMENT PORE FORMATION C5b coassembles with circulating C6 and C7 and attaches to the membrane of the target cell membrane. One C8 molecule then binds to a site on C5b and inserts into the membrane where it facilitates the insertion and subsequent polymerization of C9 molecules, which form a lytic pore known as the membrane attack complex. FIGURE 23.1 MECHANISM OF COMPLEMENT PORE FORMATION C5b coassembles with circulating C6 and C7 and attaches to the membrane of the...

Disease of Blood Pressure Regulation

Sodium Absorption

Mutations in ENaC may produce either hereditary hypotension or hypertension. To understand why this is the case, we must first consider the role of ENaC in the regulation of blood pressure. All vertebrates must maintain a constant extracellular fluid volume in the face of marked variations in water and salt uptake. A chronic increase in blood volume produces hypertension and is accompanied by an increase in the interstitial fluid volume, which results in oedema. Conversely, decreases in blood...

Weaver Mouse Kir32 Phenotype

Serca1 Defect Skeletal Muscle

Weaver mice wv wv are so called because they have an ataxic gait and thus 'weave' around when they move. They also exhibit hyperactivity and tremor. These behaviours result from a selective loss of neurones in two regions of the brain, the granule layer of the cerebellum and the substantia nigra, during development. Although the precursors of the cerebellar granule cells develop normally, they fail to differentiate and migrate into the granule layer and they die during the first two weeks of...

Charcot MarieTooth Disease Cx32

Charcot Marie Tooth Disease Cx32

Charcot-Marie-Tooth disease CMT is the most common inherited peripheral neuropathy, affecting about 1 in 2500 individuals. The disease causes progressive degeneration of the peripheral nerves. It presents in childhood or adolescence, generally beginning with a weakness in the legs, which causes difficulty in walking, and progressing later to the arms. CMT is also characterized by foot deformities, muscle wasting, ataxia, decreased tendon reflexes and distal sensory loss. The disease is both...