Temperature coefficient of membrane currents induced by noxious heat in sensory neurones in the rat

1. Membrane currents induced by noxious heat (I-heat) were studied in cultured dorsal root ganglion (DRG) neurones from newborn rats using ramps of increasing temperature of superfusing solutions. 2. I-heat was observed in about 70% of small (< 25 mu m) DRG neurones. At -60 mV, I-heat exhibited a threshold at about 43 degrees C and reached its maximum, sometimes exceeding 1 nA, at 52 degrees C (716 +/- 121 pA; n = 39). 3. I-heat exhibited a strong temperature sensitivity (temperature coefficient over a 10 degrees C temperature range (Q(10)) = 17.8 +/- 2.1, mean +/- S.D., in the range 47-51 degrees C; n = 41), distinguishing it from the currents induced by capsaicin (1 mu M), bradykinin (5 mu M) and weak acid (pH 6.1 or 6.3), which exhibited Q(10) values of 1.6-2.8 over the whole temperature range (23-52 degrees C). Repented heat ramps resulted in a decrease of the maximum I-heat and the current was evoked at lower temperatures. 4. A single ramp exceeding 57 degrees C resulted in an irreversible change in I-heat. In a subsequent trial, maximum I-heat was decreased to less than 50%, its threshold was lowered to a temperature just above that in the bath and its maximum Q(10) was markedly lower (5.6 +/- 0.8; n = 8). 5. DRG neurones that exhibited I-heat were sensitive to capsaicin. However, four capsaicin-sensitive neurones out of 41 were insensitive to noxious heat. There was no correlation between the amplitude of capsaicin-induced responses and I-heat. 6. In the absence of extracellular Ca2+, Q(10) for I-heat was lowered from 25.3 +/- 7.5 to 4.2 +/- 0.4 (n = 7) in the range 41-50 degrees C. The tachyphylaxis, however, was still observed. 7. A high Q(10) of I-heat suggests a profound, rapid and reversible change in a protein structure in the plasma membrane of heat-sensitive nociceptors. It is hypothesized that this protein complex possesses a high net free energy of stabilization (possibly due to ionic bonds) and undergoes disassembly when exposed to noxious heat. The liberated components activate distinct cationic channels to generate I-heat. Their affinity to form the complex at low temperatures irreversibly decreases after one exposure to excessive heat.