Involvement of NADPH-dependent and cAMP-PKA sensitive H+ channels in the chorda tympani nerve responses to strong acids

• Published in: Chemical senses Vol. 36; no. 4; pp. 389 - 403
• Main Authors: DeSimone, John A, Phan, Tam-Hao T, Heck, Gerard L, Ren, Zuojun, Coleman, Jamison, Mummalaneni, Shobha, Melone, Pamela, Lyall, Vijay
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.05.2011
• Subjects: Acids - metabolism; Animals; Chorda Tympani Nerve - metabolism; Cyclic AMP-Dependent Protein Kinases - metabolism; Diethyl Pyrocarbonate - pharmacology; Female; Mice; Mice, Inbred C57BL; Mice, Knockout; NADP - metabolism; NADPH Oxidases - genetics; NADPH Oxidases - metabolism; Proton Pumps - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Immunologic - genetics; Taste; Taste Buds - drug effects; Taste Buds - metabolism; Zinc - pharmacology
• ISSN: 0379-864X; 1464-3553
• DOI: 10.1093/chemse/bjq148

To investigate if chorda tympani (CT) taste nerve responses to strong (HCl) and weak (CO(2) and acetic acid) acidic stimuli are dependent upon NADPH oxidase-linked and cAMP-sensitive proton conductances in taste cell membranes, CT responses were monitored in rats, wild-type (WT) mice, and gp91(phox) knockout (KO) mice in the absence and presence of blockers (Zn(2+) and diethyl pyrocarbonate [DEPC]) or activators (8-(4-chlorophenylthio)-cAMP; 8-CPT-cAMP) of proton channels and activators of the NADPH oxidase enzyme (phorbol 12-myristate 13-acetate [PMA], H(2)O(2), and nitrazepam). Zn(2+) and DEPC inhibited and 8-CPT-cAMP, PMA, H(2)O(2), and nitrazepam enhanced the tonic CT responses to HCl without altering responses to CO(2) and acetic acid. In KO mice, the tonic HCl CT response was reduced by 64% relative to WT mice. The residual CT response was insensitive to H(2)O(2) but was blocked by Zn(2+). Its magnitude was further enhanced by 8-CPT-cAMP treatment, and the enhancement was blocked by 8-CPT-adenosine-3'-5'-cyclic monophospho-rothioate, a protein kinase A (PKA) inhibitor. Under voltage-clamp conditions, before cAMP treatment, rat tonic HCl CT responses demonstrated voltage-dependence only at ±90 mV, suggesting the presence of H(+) channels with voltage-dependent conductances. After cAMP treatment, the tonic HCl CT response had a quasi-linear dependence on voltage, suggesting that the cAMP-dependent part of the HCl CT response has a quasi-linear voltage dependence between +60 and -60 mV, only becoming sigmoidal when approaching +90 and -90 mV. The results suggest that CT responses to HCl involve 2 proton entry pathways, an NADPH oxidase-dependent proton channel, and a cAMP-PKA sensitive proton channel.