Metabolic acidosis stimulates H+ secretion in the rabbit outer medullary collecting duct (inner stripe) of the kidney.

Abstract

The outer medullary collecting duct (OMCD) absorbs HCO at high rates, but it is not clear if it responds to metabolic acidosis to increase H ϩ secretion. We measured net HCO transport in isolated perfused OMCDs taken from deep in the inner stripes of kidneys from control and acidotic (NH 4 Cl-fed for 3 d) rabbits. We used specific inhibitors to characterize the mechanisms of HCO transport: 10 M Sch 28080 or luminal K ϩ removal to inhibit P-type H ϩ ,K ϩ -ATPase activity, and 5-10 nM bafilomycin A 1 or 1-10 nM concanamycin A to inhibit H ϩ -ATPase activity. The results were comparable using either of each pair of inhibitors, and allowed us to show in control rabbits that 65% of net HCO absorption depended on

SDF1 induction by acidosis from principal cells regulates intercalated cell subtype distribution

“…Proliferation of acid-secreting α-ICs was also reported in some studies (20,21). In the outer medullary collecting tubule, there is also an increase in the amount of acid secreted by each cell in chronic acidosis (22). While, in principle, many mechanisms might be invoked to mediate this critical homeostatic response, it is clear that the machinery for regulation (Figure 1), it is likely that it was produced by the principal cell.…”

Nongenomic stimulation of vacuolar H + -ATPases in intercalated renal tubule cells by aldosterone

“…These results demonstrate that the stimulatory effect of aldosterone on vacuolar H ϩ -ATPase activity is mainly mediated by a nongenomic pathway. Good evidence exists that trafficking of vacuolar H ϩ -ATPases plays an important role in the regulation of their activity in the plasma membrane of renal cells (1,(28)(29)(30). We tested the role of such trafficking in the aldosterone-induced stimulation of vacuolar H ϩ -ATPase activity in OMCD-intercalated cells.…”

Acid incubation reverses the polarity of intercalated cell transporters, an effect mediated by hensin

“…CCDs were microdissected and microperfused as performed in this laboratory (3,20,21). Equilibration, transport, and cell pH studies were performed using Burg's solution in the perfusate and bath, containing (in mM) 120 NaCl, 25 NaHCO 3 , 2.5 K 2 HPO 4 , 2 CaCl 2 , 1.2 MgSO 4 , 5.5 D-glucose, 1 trisodium citrate, 4 sodium lactate, and 6 L-alanine, 290 ± 2 mOsm/kg H 2 O and gassed with 94% O 2 -6% CO 2 , yielding a pH 7.4 at 37°C (3,5,20). The bath was continually exchanged, except when precious Ab's were used during 3-hour incubations; in those cases, osmolality was maintained within ±1% by adding 240 µl water per hour (22) and replacing the bath and Ab's each hour.…”

“…The bath was continually exchanged, except when precious Ab's were used during 3-hour incubations; in those cases, osmolality was maintained within ±1% by adding 240 µl water per hour (22) and replacing the bath and Ab's each hour. Incubations for 3 hours in acid (pH 6.8 in both luminal and bathing solutions) and control (pH 7.4) media were described previously (3,16,20,23); incubation at pH 6.8 yields a physiology comparable to 3 days of acidosis in vivo, while that at pH 7.4 sustains net HCO 3 -secretion.…”

“…Triplicate collections of 12-15 nl of tubular fluid were made under water-saturated mineral oil and analyzed for HCO 3 - (3,20,21). When J HCO3 is greater than 0, there is net HCO 3 -absorption; when J HCO3 is less than 0, there is net HCO 3 -secretion.…”