Structure and function of two-pore-domain K+ channels:: contributions from genetic model organisms

K+ channels that possess two pore domains in each channel subunit are common in many animal tissues. Such channels are generated from large families of subunits and are implicated in several functions, including temperature sensation, responses to ischaemia, K+ homeostasis and setting the resting potential of the cell. Their activity can be modulated by polyunsaturated fatty acids, pH and oxygen, and some are candidate targets of volatile anaesthetics. However, despite their potential as targets for novel drugs for human health, comparatively little is known about the molecular basis of their diverse physiological and pharmacological properties. Genetic model organisms have considerable potential for improving our understanding of these channels. In this article, we review the contributions of some of these genetic model organisms to recent advances in our knowledge of two-pore-domain K+ channels.