Inwardly rectifying K+ channel Kir7.1 is highly expressed in thyroid follicular cells, intestinal epithelial cells and choroid plexus epithelial cells: implication for a functional coupling with Na+,K+-ATPase

Abstract

A novel inwardly rectifying K+ channel, Kir7.1, with unique pore properties, was cloned recently. Working in the field of osmoregulation, we have also identified the same human and rat channel and found that the channel is unique not only in its pore sequence but also in its dense localization in the follicular cells of the thyroid gland. Northern blot analysis revealed that the channel message was abundantly expressed in the thyroid gland and small intestine, and moderately in the kidney, stomach, spinal cord and brain. Immunohistochemistry of the rat thyroid, intestine and choroid plexus demonstrated the expression of the channel protein in the follicular cells and epithelial cells, suggesting a role in the regulation of the ion-transporting functions of these specialized cells. The unique pore properties of Kir7.1 make it a strong candidate for the hypothetical low-conductance K+ channel that is functionally coupled with Na+,K(+)-ATPase by recycling K+. We therefore further examined the co-localization of Kir7.1 and Na+,K(+)-ATPase and found that both are localized in the basolateral membrane of the thyroid follicular cell; in the choroid plexus, which is known to be unique in having Na+,K(+)-ATPase in the apical side of the epithelial cells, Kir7.1 was found in the apical membrane, implying a close functional coupling between the channel and Na+,K(+)-ATPase.

Discovery, Characterization, and Structure?Activity Relationships of an Inhibitor of Inward Rectifier Potassium (Kir) Channels with Preference for Kir2.3, Kir3.X, and Kir7.1

“…Kir7.1 is widely expressed in the brain, retinal pigment epithelial cells of the eye, the choroid plexus, and epithelial cells of the intestine, nephron, and inner ear (Krapivinsky et al, 1998; Nakamura et al, 1999; Ookata et al, 2000; Pondugula et al, 2006; Yang et al, 2008). Very little is known about the physiology of Kir7.1 due in part to the unusually small (i.e., ∼50 fS) unitary conductance of the channel.…”

A hypomorphic mutation of the gamma-1 adaptin gene (Ap1g1) causes inner ear, retina, thyroid, and testes abnormalities in mice

“…Thyroid follicular cells are polarized epithelial cells that coordinate several oppositely located surface enzyme activities, and epithelial surface asymmetry is regulated largely by intracellular sorting of newly synthesized membrane proteins at the TGN (Kuliawat et al 1995). The mislocalization of Na + /K + -ATPase, which has been localized in the baso-lateral membrane of follicular cells (Nakamura et al 1999), or other membrane proteins may underlie the thyroid pathology of Ap1g1 fgt mutant mice.…”

Molecular Insights into the Possible Role of Kir4.1 and Kir5.1 in Thyroid Hormone Biosynthesis

“…Since Kir5.1 expressed alone is limited to cytoplasm and only goes to the membrane if assembled with other Kir4.1 as already demonstrated in stomach cells, astrocytes and Müller photoreceptors [16,18,21], we believe it may play a pivotal role in trafficking and maintenance of a negative membrane potential of thyrocytes (-50 mV), although we cannot exclude other channel players, such as Kir7.1 or even other voltage-dependent potassium channels [35]. It might be possible that Kir4.1/Kir5.1 assembly in the basal lateral membrane together with the sodium-chloride channel at apical membrane permit I - uptake and its transit to lumen by creating the transepithelial voltage against the chemical I - gradient (fig.…”

“…In addition, the anion transporter SLC26A4 (pendrin) null mice, which are a model for Pendred syndrome in humans, present with thyroid goiter and deafness, and have severe hearing loss likely due to loss of Kir4.1 channels from the cochlear stria vascularis, suggesting these channels might work together in thyrocytes as well [34]. At the opposite membrane side, thyroid follicular cells and renal epithelial cells have their pumps placed close to their basolateral membrane [1,35], as happens to Kir7.1 localization that harbors the Na-K-ATPase pump in each of these epithelial cells, suggesting a function that resembles the K-recycling role of Kir1.1 and Kir4.1 channels in different tissues (fig. 2).…”