title: Involvement of NADPH-dependent and cAMP-PKA sensitive H+ channels in the chorda tympani nerve responses to strong acids.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University,1220 East Broad Street, Richmond, VA 23219, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: DeSimone
authors.forename: Tam-Hao T
authors.initials: TH
authors.lastname: Phan
authors.forename: Gerard L
authors.initials: GL
authors.lastname: Heck
authors.forename: Zuojun
authors.initials: Z
authors.lastname: Ren
authors.forename: Jamison
authors.initials: J
authors.lastname: Coleman
authors.forename: Shobha
authors.initials: S
authors.lastname: Mummalaneni
authors.forename: Pamela
authors.initials: P
authors.lastname: Melone
authors.forename: Vijay
authors.initials: V
authors.lastname: Lyall
mesh_terms: D000143:Acids / Q000378:metabolism*; D000818:Animals; D002814:Chorda Tympani Nerve / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004047:Diethyl Pyrocarbonate / Q000494:pharmacology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009249:NADP / Q000378:metabolism*; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D017494:Proton Pumps / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000235:genetics; D013649:Taste; D013650:Taste Buds / Q000187:drug effects / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology
chemical_list: D000143:Acids; C105949:Pirb protein, mouse; D017494:Proton Pumps; D011971:Receptors, Immunologic; D009249:NADP; D019255:NADPH Oxidases; D017868:Cyclic AMP-Dependent Protein Kinases; D015032:Zinc; D004047:Diethyl Pyrocarbonate