Role of a receptor tyrosine kinase in the HCO 3 ‐induced inhibition of HCO 3 reabsorption by rabbit S2 proximal tubule

Previous work showed that: (1) Proximal tubules (PTs) respond to increases in basolateral (BL) [CO 2 ] or [HCO 3 ] by, respectively, stimulating or inhibiting HCO 3 reabsorption ( J HCO3 ), suggesting the presence of CO 2 /HCO 3 sensors near the basolateral membrane. (2) Studies with PD168393 (blocks erbB1 via alkylating a Cys in the ATP‐binding pocket) and BPIQ‐I (competes with ATP) suggest that the CO 2 sensitivity of J HCO3 requires an active receptor tyrosine kinase (RTK), probably erbB1. Here, I hypothesize an active RTK also is required for the HCO 3 sensitivity of J HCO3 . I perfused the lumen of an isolated rabbit S2 PT with 5% CO 2 /22 mM HCO 3 solution. Adding BL 35 nM PD168393 significantly decreased "baseline" J HCO3 (i.e. [HCO 3 ] BL = 22 mM, [CO 2 ] BL = 5%, pH BL = 7.4) from 69 ± 3 (n = 32) to 43 ± 4 pmol mm −1 min −1 ("pmm", n = 6, P < 0.0001). Using an out‐of‐equilibrium (OOE) solution to decrease [HCO 3 ] BL to 0 mM, I found that BL 35 nM PD168393 decreased J HCO3 from 103 ± 6 (n = 7) to 62 ± 7 pmm (n = 6, P < 0.0006) at a fixed [CO 2 ] BL of 5% and pH BL of 7.4. Using OOE solutions to increase [HCO 3 ] BL to 44 mM, I found that BL 35 nM PD168393 had no effect on the already‐low J HCO3 (n = 7, P <0.79). Thus, BL 35 nM PD168393 decreased baseline J HCO3 by 37%, reduced the J HCO3 response at 0 mM HCO 3 , and eliminated the response at 44 mM. An active RTK, perhaps erbB1, plays a central role in both CO 2 and HCO 3 signaling regulating H + secretion by PTs. (Supported by AHA SDG 0735432N)