| Even at rest, the neuron is working to pump ions along ionic gradients
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An 18-year-old male awoke in the night with intense weakness of the proximal muscles of his arms and legs. Before retiring he had consumed a meal of pasta and cake. His brother and father had previously been similarly affected. He was taken to the emergency room of the local hospital where the weak limbs were noted to be hypotonic with depressed tendon reflexes. Serum concentration of potassium was mildly reduced at 2.9 mmol/L (normal 3.5-5.5). By the next day he had fully recovered and serum potassium had risen spontaneously to normal levels. A further attack of paralysis was induced by an infusion of intravenous glucose thereby confirming a diagnosis of familial periodic paralysis. |
| Comment. Hypokalaemic periodic paralysis is inherited as a Mendelian dominant and results from a mutation in the gene encoding the l-type calcium channel. Genetic diseases that affect ion channel function are called channelopathies. (See also Chapter 7.) |
| The 'resting' neuron is, nevertheless, continually pumping sodium out of the cell and potassium in, through ion channels. During an action potential, there is a momentary reversal of these ionic movements, such that sodium enters the cell and potassium then leaves, effectively repolarizing the resting
membrane. Mutations of sodium channels can occur at different sites and give rise to hyperkalemic periodic paralysis. The negative ion, chloride, moves through separate channels, which are implicated in specific pathologic states such as myotonia.
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| Calcium ions have an important role in the synchronization of neuronal activity
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| The movement of calcium ions within cells often provides a 'trigger' for the cells to synchronize an activity such as synaptic release of neurotransmitter; this synchronization of movement is also seen to have a prominent role in the sarcoplasmic reticulum of muscle (see Chapter 19). Within the central nervous system, the Lambert-Eaton syndrome is a disease that affects predominantly the P/Q subtype of calcium channels, in an example of molecular mimicry. The patient may have a primary oat-cell carcinoma of the lung; the immune system responds by making antibodies against these malignant cells. However, the malignancy and the calcium channels possess a common epitope, the effect of which is that the immune response causes the release of neurotransmitter to be blocked at the presynaptic site. This is analogous to, but nevertheless can be clearly distinguished from, the condition in myasthenia gravis, in which the block is postsynaptic.
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| It is also worth noting that blockade of the presynaptic release of neurotransmitter may be usefully exploited by therapeutic application of botulinus toxin (a protein derived from anerobic bacteria), which contains enzymes to hydrolyze the presynaptic proteins involved in release of neurotransmitters.
This toxin is used in special cases of spasticity such as torticollis, in which the patient can be relieved of the excessive contractures of the neck muscles, which turn the head chronically to one side and thus cause pain and distraction if untreated.
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