Exploring the physiological role of inward rectifying potassium channels in arthropod disease vectors

Novel target sites to control arthropod disease vectors are needed to enhance the current mechanisms of vector-borne disease control. To combat the growing levels of resistance, our group is exploring inward rectifying potassium (Kir) channels as viable target sites for vector control.  Although the physiological roles of Kir channels in insects are significantly less understood when compared to mammals, it has been shown that they play important physiological roles in osmoregulation, immunity, development, and ion transport in insect Malpighian tubules. Kir channels are expressed in the insect Malpighian tubules and have been shown to constitute a critical conductance pathway that drives the functionality of the tubules.  Inhibition of the Kir channels severely hinders epithelial transport and fluid secretion across the membrane of the Malpighian tubules, which prevents proper function of the tubules and precludes urine formation and blood meal digestion.  The greater majority of arthropods utilize the Malpighian tubules for osmoregulation, but ticks are unique in that the salivary gland is the organ responsible for osmoregulation as well as pathogen transmission.  The salivary gland and Malpighian tubules are similar in cell makeup and functionality, which raises the intriguing possibility that Kir channels have similar physiological roles in the two tissues. Interestingly, Kir channels play a critical role in salivary gland function of herbivorous mammals and preliminary data show that mRNA expression of Kir channel constructs are highly upregulated in Drosophila and mosquito salivary glands, suggesting Kir channels constitute a critical conductance pathway in the salivary glands as well.  This work aimed to characterize the role of Kir channels in tissues that are critical to insect survival and/or pathogen transmission and determine the potential for the development of molecules targeting these potassium channels.  Bioassay and electrophysiological data to determine the physiological relevance of these channels will be presented and implications for arthropod control will be discussed.