Occurrence of sodium channels in epithelia

It is important to realise that sodium channels in epithelia are different from those in excitable membranes. One clear piece of pharmacological evidence for this point of view is that epithelial sodium channels are relatively unaffected by TTX in high concentrations [147,148]. Furthermore, it is likely that there is more than one type of sodium channel in epithelia. For example, there are a number of pyrazine and pteridine compounds which block sodium transport by blocking sodium entry into the cells of the distal kidney tubule but do not block sodium entry into cells of the proximal tubules. 

From the point of view taken in this review, only those epithelia having sodium channels which can be blocked by defined chemical compounds, particularly the pyrazine carboxamides, will be discussed. 

As a general rule, channels blocked by the pyrazine compounds are found only in tight but not leaky epithelia. Thus pyrazine carboxamides block sodium entry into the cells of the kidney distal tubule [149], salivary duct [150], colon [ISl] and epididymis [152], but not into the cells of the small intestine of kidney proximal tubule. Sodium channels sensitive to pyrazine carboxamides are not confined either to epithelia or to mammalian cells. For example, sodium entry into the cells of frog skin epithelium [153], toad urinary bladder [154], chicken coprodeum, fish gills of some species [ISS], body wall of the leech [155] and crustacean gills [155] are also sensitive. In addition, there are reports that sodium entry sites in ova [3] and erythrocytes [156] are also susceptible to the effects of the pyrazine derivatives. 

The wide distribution of sensitive tissues suggests that this type of channel is of considerable evolutionary antiquity as are the voltage-sensitive sodium channels of excitable membranes. Furthermore, throughout the remaining sections of this review, it will become clear that there are some, at least superficial, similarities between sodium channels in excitable membranes and those in epithelia. 

Initially, screening tests for putative diuretics are generally carried out on rats. There are two types of tests which are of interest here. First, using saline- 

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