Effect of the putative Ca2+-receptor agonist Gd3+ on the active transepithelial Na+ transport in frog skin.
In this communication we show that Gd3+ acts as an activator of the apical sodium channel (ENaC) in frog skin epithelia. Application of Gd3+ to the apical solution of frog skin epithelia increased the Na+ absorption measured as the amiloride-inhibitable short-circuit current (Isc). The stimulation was dose dependent with a concentration for half-maximal stimulation (EC50) of 0.023 mM. The change in Isc was found to correlate with the net Na+ flux, confirming that Gd3+ enhances Na+ absorption. By monitoring the cellular potential (Vsc) with microelectrodes during addition of Gd3+, it was found that Vsc depolarized as Isc rose, indicating that Gd3+ affects apical Na+ permeability (PNa). This was confirmed by measuring the I/V relations of the apical membrane. In the presence of benzimidazolylguanidin (BIG), a drug known to abolish the Na+ self-inhibition, Gd3+ had no effect on Isc. The Na+ self-inhibition was investigated using fast changes of the apical Na+ concentration on K+-depolarized epithelia. BIG was found to abolish the Na+ self-inhibition and to activate the basal Na+ transport, whereas Gd3+ only activated the basal Na+ transport but had no effect on the self-inhibition. These results indicate the existence of an alternative nonhormonal mechanism to Na+ self-inhibition, via which both Gd3+ and BIG act, possibly components of the Na+ feedback inhibition system.
Friis
S
S
August Krogh Institute, The University of Copenhagen, Universitetsparken 13, DK-21200 Copenhagen, Copenhagen, Denmark.
Nielsen
R
R
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000378:metabolism*; D005246:Feedback / Q000502:physiology; D005260:Female; D005682:Gadolinium / Q000378:metabolism* / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D023421:Models, Animal; D008954:Models, Biological; D018408:Patch-Clamp Techniques / Q000379:methods; D011893:Rana esculenta; D012867:Skin / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism / Q000493:pharmacokinetics*; D015222:Sodium Channels / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*
D006146:Guanidines; D015222:Sodium Channels; C032996:2-benzimidazolylguanidine; D012964:Sodium; D005682:Gadolinium; D000254:Sodium-Potassium-Exchanging ATPase