Potassium channels--multiplicity and challenges.

The development of our knowledge of the function, structure and pharmacology of K(+) channels is briefly outlined. This is the most diverse of all the ion channel families with at least 75 coding genes in mammals. Alternative splicing as well as variations in the channel subunits and accessory proteins that co-assemble to form the functional channel add to the multiplicity. Whereas diversity of this order suggests that it may be possible to develop new classes of drug, for example, for immunomodulation and some diseases of the central nervous system, the ubiquity of K(+) channels imposes stringent requirements for selectivity. Animal toxins from the snake, bee and scorpion provide useful leads, though only in a few instances (e.g. with apamin) it has been possible to produce non-peptidic analogues of high potency. The scale of the resources needed to identify, and characterize fully, specific K(+) channel as targets and then develop modulators with the required selectivity presents a challenge to both academic and applied pharmacologists.