Defects of
sodium channels
Different molecular lesions at various
sites of the sodium channel pores can give rise to hyperkalemic
periodic paralysis. As this name suggests, the patient has
intermittent muscle weakness, during which time the serum potassium
concentration is increased. This is caused by an imbalance of
cationic movements in which sodium enters the cell and potassium
leaves it. For these patients, the abnormal flux of sodium into the
muscle is not correctly regulated with its counterflux of potassium
ions.
Acetylcholine (Ach) is the neurotransmitter that has been
best studied. As a model system, this transmitter can have two rather
different effects, depending upon its site of origin within the nervous
system (i.e. central or peripheral): those effects originally demonstrated
by experiments with nicotine are characteristic of the nicotinic
receptor, whereas those demonstrated with muscarine characterize the
muscarinic receptor. Modern developments in pharmacology and DNA
technology have produced a complex picture of the agonists and antagonists
associated with the regional actions of ACh (Fig. 39.3). The
classical antagonist of the muscarinic effect is atropine, and the
best-studied blocker for the nicotinic receptor is the poisonous snake
venom, a-bungarotoxin. |
| In
myasthenia gravis, autoantibodies are formed against the nicotinic
receptor for ACh. However, by blocking the hydrolysis of ACh, for example
by means of the drug edrophonium (which inhibits the hydrolytic enzyme,
acetylcholinesterase), the concentration of ACh can be effectively
increased (see Chapter 40). |
| |
