Chloride channels in the apical membrane of thyroid epithelial cells are regulated by cyclic AMP

Abstract

Porcine thyroid epithelial cells cultured as a monolayer with their apical membranes facing the medium are known to absorb Na+ and to secrete the anions Cl- and HCO3-. Chloride channels were found in the apical membrane, and displayed a reversal potential close to the resting membrane potential, linear current-voltage relationships, a conductance at physiological temperature of 6.5 pS, and a small but significant permeability to HCO3-. Stimulation of ion transport with prostaglandin E2 or 8-(4-chlorophenylthio) adenosine 3':5'-cyclic monophosphate promoted activation of Cl- channels in cell-attached patches, and excised patches were reactivated by exposure of their cytoplasmic surface to protein kinase A and ATP. Physiological temperatures were necessary for activation of Cl- channels in cell-attached patches. The channels exhibited sub-states with a conductance exactly half that of the full unit conductance, suggesting a dual-barrelled channel structure. It is concluded that the apical membrane of thyroid epithelial cells contains cyclic AMP-activated Cl- channels controlling anion transport.

Developmental delays consistent with cochlear hypothyroidism contribute to failure to develop hearing in mice lacking Slc26a4/pendrin expression

“…Primary cultures generate a lumen-negative transepithelial potential that is similar in magnitude to the transepithelial potential that we observe in situ in the murine thyroid. The lumennegative transepithelial potential is most likely generated by a combination of K ϩ channels expressed in the basolateral membrane and Na ϩ and Cl Ϫ channels expressed in the apical membrane (9,10,36). A possible cause for the reduced transepithelial potential in mice lacking pendrin is an inhibition of the apical Na ϩ channels or the basolateral K ϩ channels by an acidic cytosolic pH (47).…”

Thyroid iodide efflux: a team effort?

“…The small single channel conductance (∼5.5 pS) and ohmic current–voltage relationship aligned well with CFTR's biophysical profile (Champigny et al 1990). Similar protein kinase A‐regulated Cl − channels in polarized primary thyroid cultures displayed permeability to HCO 3 − as well as Cl − (Bourke et al 1995). Thus, CFTR‐like anion channels have been measured in apical membranes of polarized primary thyroid cells.…”

UTP‐preferring P2 receptor mediates inhibition of sodium transport in porcine thyroid epithelial cells

“…Understanding of the regulation of such a complex system remains elusive, however. Activation of the cyclic AMP‐dependent protein kinase A pathway results in immediate (seconds) activation of Cl − secretion ( Armstrong et al ., 1992 ), through 6 pS Cl − channels on the apical membrane ( Bourke et al ., 1995 ). Agents promoting cyclic AMP accumulation cause a slower (minutes) increase in short‐circuit current due to Na + absorption ( Armstrong et al ., 1992 ).…”

“…We have documented the activation of parts of this system by adenosine 3′,5′‐cyclic monophosphate (cyclic AMP) ( Bourke et al ., 1990 ; Armstrong et al ., 1992 ) and inhibition by Ca 2+ ( Manley et al ., 1988 ). The bidirectional transport system involves a variety of cation channels and a Cl − channel on the apical membrane of the cells ( Bourke et al ., 1995 ; 1996 ), with an NaK2Cl symporter and Na + /K + ATPase on the basolateral membrane ( Armstrong et al ., 1992 ).…”