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This Article Full Text Full Text (PDF) All Versions of this Article: 95/4/2466    most recent 00861.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Jiang, N. Articles by Cooper, B. Y. Search for Related Content PubMed PubMed Citation Articles by Jiang, N. Articles by Cooper, B. Y.

Proton Sensitivity Ca²⁺ Permeability and Molecular Basis of Acid-Sensing Ion Channels Expressed in Glabrous and Hairy Skin Afferents

¹Department of Oral Surgery and Diagnostic Sciences, Division of Neuroscience, J. H. Miller Health Center, University of Florida College of Dentistry and McKnight Brain Institute, ²Department of Physiological Sciences, College of Veterinary Medicine and University of Florida, McKnight Brain Institute, and ³Department of Neuroscience, College of Medicine and University of Florida, McKnight Brain Institute, Gainesville, Florida

Submitted 17 August 2005; accepted in final form 20 December 2005

We contrasted the physiology and peripheral targets of subclassified nociceptive and nonnociceptive afferents that express acid-sensing ion channel (ASIC)–like currents. The threshold for current activation was similar in eight distinct cell subclasses regardless of functional modality (pH 6.8). When potency was determined from concentration–response curves, nonnociceptors exhibited currents with significantly greater potency than that of all but one class of nociceptors (pH₅₀ = 6.54 and 6.75 vs. 6.20–6.34). In nonnociceptive cells, acid transduction was also confined to a very narrow range (0.1–0.3 vs. 0.8–1.4 pH units for nociceptors). Simultaneous whole cell recording and ratiometric imaging of three peptidergic nociceptive classes were consistent with the expression of Ca²⁺-permeable ASICs. Sensitivity to psalmotoxin and flurbiprofen indicated the presence of Ca²⁺-permeable ASIC1a. Immunocytochemistry on these subclassified populations revealed a differential distribution of five ASIC proteins consistent with Ca²⁺ permeability and differential kinetics of proton-gated currents (type 5: ASIC1a, 1b, 2a, 2b, 3; type 8a: ASIC1a, 1b, 3; type 8b: ASIC1a, 1b, 2a, 2b, 3). Using DiI tracing, we found that nociceptive classes had discrete peripheral targets. ASIC-expressing types 8a and 9 projected to hairy skin, but only types 8a and 13 projected to glabrous skin. Non-ASIC–expressing types 2 and 4 were present only in hairy skin. We conclude that ASIC-expressing nociceptors differ from ASIC-expressing nonnociceptors mainly by range of proton reactivity. ASIC- as well as non-ASIC–expressing nociceptors have highly distinct cutaneous targets, and only one class was consistent with the existence of a generic C polymodal nociceptor (type 8a).

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