Autoregulation of apical membrane Na+ permeability of tight epithelia. Noise analysis with amiloride and CGS 4270.
Noise analysis of the Na+ channels of the apical membranes of frog skin bathed symmetrically in a Cl-HCO3 Ringer solution was done with amiloride and CGS 4270. Tissues were studied in their control states and after inhibition of transepithelial Na+ transport (Isc) by addition of quinine or quinidine to the apical solution. A critical examination of the amiloride-induced noise indicated that the single channel Na+ currents (iNa) were decreased by quinine and quinidine, probably because of depolarization of apical membrane voltage. Despite considerable statistical uncertainty in the methods of estimation of the Na+ channel density with amiloride-induced noise (NA, see text), the striking observation was a large increase of NA with amiloride inhibition of the rate of Na+ entry into the cells. NA was increased to 406% of control, whereas Isc was inhibited to 8.6% of control by 6 microM amiloride. Studies were done also with the Na+ channel blocker CGS 4270. Noise analysis with this compound was advantageous, permitting iCGSNa and NCGS to be measured in individual tissues with a relatively small inhibition of Isc. As with amiloride, inhibition of Isc with CGS 4270 caused large increases of the Na+ channel density (approximately 200% at approximately 35% inhibition of the Isc). Quinine and quinidine caused an approximately 50% increase of Na+ channel density while inhibiting iNa by approximately 60-70%. As inhibition of Na+ entry leads to an increase of Na+ channel density, a mechanism of autoregulation appears to be a major factor in adjusting the apical membrane Na+ permeability of the cells.
F J
FJ
Abramcheck
W
W
Van Driessche
S I
SI
Helman
D000584:Amiloride; D000818:Animals; D002463:Cell Membrane Permeability; D004560:Electricity; D004848:Epithelium / Q000378:metabolism; D006706:Homeostasis; D007473:Ion Channels / Q000187:drug effects; D010827:Physiology / Q000295:instrumentation; D011719:Pyrazines; D011802:Quinidine / Q000494:pharmacology; D011803:Quinine / Q000494:pharmacology; D011894:Rana pipiens; D012867:Skin / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
D007473:Ion Channels; D011719:Pyrazines; C025936:3-(3-amino-1,2,4-oxadiazol-5-yl)-5-chloro-2,6-pyrazinediamine; D000584:Amiloride; D012964:Sodium; D011803:Quinine; D011802:Quinidine