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The putative role of vanilloid receptor‐like protein‐1 in mediating high threshold noxious heat‐sensitivity in rat cultured primary sensory neurons
Author(s) -
Ahluwalia Jatinder,
Rang Humphrey,
Nagy Istvan
Publication year - 2002
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2002.02231.x
Subject(s) - chemistry , capsazepine , biophysics , receptor , noxious stimulus , membrane potential , population , trpv1 , transient receptor potential channel , biochemistry , nociception , biology , medicine , environmental health
High threshold noxious heat‐activated currents and vanilloid receptor‐like protein‐1 expression were studied in rat cultured primary sensory neurons to find out the molecule(s) responsible for high threshold noxious heat‐sensitivity. The average temperature threshold and amplitude of high threshold noxious heat‐activated currents were 51.6 ± 0.13 °C and −2.0 ± 0.1nA (at a holding potential of −60 mV), respectively. The current–voltage relationship of high threshold noxious heat‐activated currents was linear at positive membrane potentials, while it showed a weak inward rectification at negative membrane potentials. The average reversal potential measured in control intracellular and extracellular solutions was 4.5 ± 0.9 mV ( n = 6). Ionic substitutions revealed that the high threshold noxious heat‐activated current is a nonselective cationic current with calculated ionic permeabilities of Cs + : Na + : Ca 2+ (1 : 1.3 : 4.5). Consecutive stimuli reduced the heat threshold from 52.2 ± 1 to 48.4 ± 1.4 °C and then to 44 ± 0.7 °C ( n = 3). High threshold noxious heat‐activated currents could dose‐dependently and reversibly be reduced by ruthenium red (100 n m −10 µ m ) but not by capsazepine (10 µ m ). The average longest diameter of high threshold noxious heat‐sensitive neurons was 31.48 ± 0.5 µm (A = ≈778 µm 2 ; n = 77). Twenty‐three percent of the total neuronal population expressed vanilloid receptor‐like protein‐1. The average area of the vanilloid receptor‐like protein‐1‐immunopositive cells was 1696 ± 65.3 µm 2 (d = ∼46 µm). Vanilloid receptor‐like protein‐1‐expressing neurons did not express the vanilloid receptor 1. Comparison of our data with results obtained in vanilloid receptor‐like protein‐1‐expressing non‐neuronal cells and previous immunohistochemical findings suggests that high threshold noxious heat‐activated currents are produced by vanilloid receptor‐like protein‐1 and that high threshold heat‐sensitive dorsal root ganglion neurons are the perikarya of type I noxious heat‐sensitive fibers.