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Model of chloride‐bicarbonate counter‐movement in CO 2 ‐sensitive avian intrapulmonary chemoreceptors (1092.2)
Author(s) -
Lonjaret JeanGuillaume,
Bassett Peter,
Meehan Shane,
Sheridan Krystal,
Hempleman Steven
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1092.2
Subject(s) - dids , bicarbonate , chemistry , bumetanide , carbonic anhydrase , efflux , biophysics , antiporter , niflumic acid , ion transporter , transporter , chloride channel , transmembrane protein , transduction (biophysics) , membrane potential , biochemistry , membrane , enzyme , biology , receptor , organic chemistry , gene
Our working model of IPC CO2 transduction (AJP, 279: R1988‐1995, 2000) posited intracellular H+ as the transduced variable, with H+ critically dependent on carbonic anhydrase, rapid H+ buffering, and transmembrane H+ exchange. Empirical testing has refined the model (and vice versa), and recent experiments suggest that Cl‐ ions, currently ignored in model, have a significant role in IPC CO2 transduction. In‐vivo Cl‐ ion channel blockers (eg. niflumic acid), and Cl‐ transport inhibitors (bumetanide, furosemide, DIDS) all significantly affect IPC response to CO2. We therefore modified the IPC model to include rapid, bidirectional HCO3‐/Cl‐ channel and transporter fluxes, and cation‐coupled Cl‐ transport, similar to the HCO3‐/Cl‐ shift in RBCs. Net Cl‐ and HCO3‐ transmembrane fluxes during CO2 stimulation were constrained by macroscopic electroneutrality. The new model predicts net Cl‐ influx and HCO3‐ efflux across IPC membrane when PCO2 is high, and net Cl‐ efflux and HCO3‐ influx when PCO2 is low; both affect IPC excitability. A system linked differential equations was formulated, then solved using Berkeley Madonna 8.3.18 software. Results indicate that large, phasic transmembrane HCO3‐/Cl‐ fluxes are required for normal IPC CO2 transduction. Grant Funding Source : supported by NIH 2R15 HL087269‐02