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1 Oral and Maxillofacial Surgery and Diagnostic Sciences, University of Florida College of Dentistry, Gainesville, Florida, USA
2 Neuroscience, University of Florida College of Medicine, Gainesville, Florida, USA
3 Physiological Sciences, University of Florida College of Veterinary Medicine, Gainesville, Florida, USA
* To whom correspondence should be addressed. E-mail: bcooper{at}dental.ufl.edu.
We contrasted the physiology and peripheral targets of subclassified nociceptive and non-nociceptive afferents that express ASIC-like currents. The threshold for current activation was similar in 8 distinct cell subclasses regardless of functional modality (pH 6.8). When potency was determined from concentration response curves, non-nociceptors exhibited currents with significantly greater potency than all but one class of nociceptors (pH50 = 6.54 and 6.75 vs. 6.20-6.34). In non-nociceptive 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 was 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 5 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 type 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 non-nociceptors 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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