Aldosterone control of the density of sodium channels in the toad urinary bladder

Abstract

Near-instantaneous current-voltage relationships and shot-noise analysis of amiloride-induced current fluctuations were used to estimate apical membrane permeability to Na (PNa), intraepithelial Na activity (Nac), single-channel Na currents (i) and the number of open (conducting) apical Na channels (N0), in the urinary bladder of the toad (Bufo marinus). To facilitate voltage-clamping of the apical membrane, the serosal plasma membranes were depolarized by substitution of a high KCl (85 mM) sucrose (50 mM) medium for the conventional Na-Ringer's solution on the serosal side. Aldosterone (5 X 10(-7) M, serosal side only) elicited proportionate increases in the Na-specific current (INa and in PNa, with no significant change in the dependence of PNa on mucosal Na (Nao). PNa and the control of PNa by aldosterone were substrate-dependent: In substrate-depleted bladders, pretreatment with aldosterone markedly augmented the response to pyruvate (7.5 X 10(-3) M) which evoked coordinate and equivalent increases in INa and PNa. The aldosterone-dependent increase in PNa was a result of an equivalent increase in the area density of conducting apical Na channels. The computed single-channel current did not change. We propose that, following aldosterone-induced protein synthesis, there is a reversible metabolically-dependent recruitment of preexisting Na channels from a reservoir of electrically undetectable channels. The results do not exclude the possibility of a complementary induction of Na-channel synthesis.

Regulation of Na channels of the rat cortical collecting tubule by aldosterone.

“…A primary action of the hormone is the increase in Na permeability of the apical membrane of these cells, leading to increased Na reabsorption. This has been demonstrated both with electrical measurements on intact epithelia (Nagel and Crabb6, 1980;Palmer, Li, Lindemann, and Edelman, 1982;Lewis and Wills, 1983;Sansom and O'Neil, 1985) and with Na fluxes into isolated membrane vesicles (Asher and Garty, 1988). There is, however, relatively little known about the action of aldosterone at the single channel level.…”

“…There is, however, relatively little known about the action of aldosterone at the single channel level. Palmer et al (1982) used noise analysis to show that the increase in permeability in the toad bladder was the result of an increase in the apparent number of conducting channels, with no change in the single channel current. More recently, Kemendy et al (Ling, Kemendy, Kokko, Hinton, Marunaka, and Eaton, 1990;Kemendy, Kleyman, and Eaton, 1992) have shown in A6 cells that a major effect of the hormone is to increase Na channel open probability (Po).…”

Apical membrane permeability and kinetic properties of the sodium pump in rabbit urinary bladder.

“…in toad urinary bladder, Palmer, Li, Lindemann & Edelman 1982;hen coprodaeum, Christensen & Bindslev, 1982; rabbit descending colon, Thompson, Suzuki & Schultz, 1982;Lewis, Eaton & Diamond, 1976). More recent evidence from current fluctuation analysis, suggests that the increase in Na+ transport is a consequence of the addition or activation of Na+ channels (Christensen & Bindslev, 1982;Palmer et al 1982;Zeiske, Wills & Van Driessche, 1982;Loo, Lewis & Diamond, 1982). With the ability to measure intracellular Na+ and K+ activities and membrane conductances we now have been able to determine the selective permeability of the apical membrane in the presence and absence of amiloride, and before and after aldosterone stimulation.…”

Correlates of aldosterone-induced increases in Cai2+ and Isc suggest that Cai2+ is the second messenger for stimulation of apical membrane conductance.

“…This expression of hormone action is initiated only after a latent period of 60-90 min, and is dependent on mRNA (4) and protein synthesis (5). Experiments in intact tissue and cultured amphibian cells suggest that the aldosterone-induced increase in electrogenic sodium transport can be viewed as involving an early phase lasting [6][7][8][9][10][11][12] h, and a delayed or chronic phase, that persists as long as agonist is present. The early phase is characterized by a gradual increase in apical membrane conductance for sodium, due to activation of amiloride-sensitive sodium This work has previously been reported in preliminary form.…”

“…During the chronic phase, hormone action stimulates the production of a and ,B subunits ofNa-K-ATPase (8). Physiological studies have demonstrated both a higher density of activated sodium channels, with unchanged current amplitude per channel, in apical membrane (9), and a higher turnover ofsodium at the basolateral membrane in epithelium exposed chronically to aldosterone (1O).…”