Proton sensitivity Ca2+ permeability and molecular basis of acid-sensing ion channels expressed in glabrous and hairy skin afferents.
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).
Jiang
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Department of Oral Surgery and Diagnostic Sciences, Division of Neuroscience, J.H. Miller Health Center, University of Florida College of Dentistry, Gainesville, FL 32610, USA.
Rau
K K
KK
Johnson
R D
RD
Cooper
B Y
BY
D062565:Acid Sensing Ion Channels; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000032:analysis / Q000502:physiology; D002463:Cell Membrane Permeability / Q000502:physiology*; D062626:Degenerin Sodium Channels; D004594:Electrophysiology; D053503:Epithelial Sodium Channels; D005727:Ganglia, Spinal / Q000737:chemistry / Q000502:physiology; D006197:Hair; D007150:Immunohistochemistry; D007473:Ion Channels / Q000032:analysis / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000502:physiology*; D009475:Neurons, Afferent / Q000737:chemistry / Q000502:physiology*; D009619:Nociceptors / Q000737:chemistry / Q000502:physiology; D018408:Patch-Clamp Techniques; D011522:Protons; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000294:innervation*; D015222:Sodium Channels / Q000032:analysis / Q000502:physiology*
D062565:Acid Sensing Ion Channels; C568425:Asic2 protein, rat; D015220:Calcium Channels; D062626:Degenerin Sodium Channels; D053503:Epithelial Sodium Channels; D007473:Ion Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011522:Protons; D015222:Sodium Channels; D002118:Calcium