Mechanism of Inhibition of Transepithelial Sodium Transport in Frog Skin by Quinine and Quinidine (Noise Analysis, Cgs 4270, Basolateral Membrane)

Studies were done with intracellular microelectrodes to assess the effects of quinine and quinidine on the electrophysiological characteristics of the Na('+) transporting epithelial cells of frog skin. Under control conditions with tissues bathed symmetrically with a Cl-HCO(,3) Ringer solution and short-circuited continuously, quinine caused a rapid inhibition of the I(,sc) while quinidine caused inhibition but only after a transient stimulation of the I(,sc). Despite small transient changes of apical membrane slope resistance, R(,o), the principle and consistent effects of these drugs occurred at the basolateral membranes of the cells. The drugs caused large rapid (a few minutes) increases of basolateral membrane resistance, R(,i), with little or relatively small increases of its emf, E(,i). Thereafter, while R(,i) remained above control values, the E(,i) in quinine treated epithelia fell markedly. After quinidine E(,i) either remained essentially constant while R(,i) increased continually for about 30 minutes, or E(,i) and R(,i) were changed as in tissues treated with quinine. Similar results were obtained with epithelia treated with amiloride. Consistent with these results quinine and quinidine caused a marked inhibition of unidirectional ('42)K flux across the basolateral membrane and hence caused a large decrease of P(,K). In the absence of any demonstrable conductance to Na('+) or Cl('-) at this membrane, the mechanism underlying the depolarization of the E(,i) caused by these agents remains unknown. Studies with fluctuation analysis indicated that the single channel Na('+) currents (i(,Na)) were decreased by quinine and quinidine due most likely to depolarization of apical membrane voltage. Interestingly we observe large increases of the Na('+) channel density (N('A)) with amiloride inhibition of the I(,sc). N('A) was increased to 406% of control while I(,sc) was inhibited to 8.6% of control at 6 (mu)M amiloride. Studies with CGS 4270 permitted (i(,Na))('CGS) and N('CGS) to be measured in individual tissues. As with amiloride, inhibition of I(,sc) with CGS 4270 caused large increases of the Na('+) channel density ((TURN) 200% at (TURN) 35% inhibition of the I(,sc)). Quinine and quinidine caused about a 50% increase of Na('+) channel density while inhibiting the i(,Na) by about 60-70%. As inhibition of Na('+) entry leads to increases of Na('+) channel density, a mechanism of autoregulation appears to be a major factor in adjusting the apical membrane Na('+) permeability of the cells.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Physiology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2014

Author dc:creator

• Abramcheck, Frank John

• Biology, Animal Physiology

Identifier

(UMI)AAI8502052

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/71430