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The effects of capsaicin and acidity on currents generated by noxious heat in cultured neonatal rat dorsal root ganglion neurones

1 The effects of capsaicin, acidic pH, ATP, kainate and GABA on currents generated by noxious heat were studied in cultured dorsal root ganglion (DRG) neurones (< 20 μm in diameter) isolated from neonatal rats. The patch clamp technique was used to record membrane currents or changes of membrane potential. 2 In agreement with previous results, inward membrane currents (Iheat) induced by a 3 s ramp of increasing temperature from room temperature (≈23 °C) to over 42 °C varied greatly between cells (‐100 pA to −2.4 nA at 48 °C) and had a temperature coefficient (Q10) > 10 over the range of 43‐52 °C. 3 Capsaicin potentiated the heat‐induced current even when capsaicin, at room temperature, had little or no effect on its own. In cells in which capsaicin induced no or very small membrane current at room temperature (< 50 pA), Iheat exhibited detectable activation above 40 °C and increased 5.1 ± 1.1 (n= 37) and 6.3 ± 2.0 (n= 18) times at 0.3 and 1 μM capsaicin, respectively. 4 A rapid decrease in extracellular pH from 7.3 to 6.8, 6.3 or 6.1 produced an inward current which inactivated in ≈5 s either completely (pH 6.8 or 6.3) or leaving a small current (≈50 pA) for more than 2 min (pH 6.1). After inactivation of the initial low pH‐induced current, Iheat at 48 °C increased 2.3 ± 0.4 times at pH 6.8, 4.0 ± 0.6 times at pH 6.3 and 4.8 ± 0.8 times at pH 6.1 with a Q10 > 10 (n= 16). 5 ATP (n= 22), kainate (n= 7) and GABA (n= 8) at 100 μM, produced an inactivating inward current in all heat‐sensitive DRG neurones tested. During inactivation and in the presence of the drug, Iheat was increased slightly with ATP and unaffected with kainate and GABA. These agents apparently do not directly affect the noxious heat receptor. 6 The results indicate a novel class of capsaicin‐sensitive cells, in which capsaicin evokes no or very small inward current but nevertheless increases sensitivity to noxious heat.