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

Abstract

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 μm) DRG neurones. At -60 mV, I(heat) exhibited a threshold at about 43°C and reached its maximum, sometimes exceeding 1 nA, at 52°C (716 ± 121 pA; n = 39). 3. I(heat) exhibited a strong temperature sensitivity (temperature coefficient over a 10°C temperature range (Q10)= 17.8 ± 2.1, mean ± S.D., in the range 47-51°C; n = 41), distinguishing it from the currents induced by capsaicin (1 μM), bradykinin (5 μM) and weak acid (pH 6.1 or 6.3), which exhibited Q10 values of 1.6-2.8 over the whole temperature range (23-52°C). Repeated 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°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 Q10 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+, Q10 for I(heat) was lowered from 25.3 ± 7.5 to 4.2 ± 0.4 (n = 7) in the range 41-50°C. The tachyphylaxis, however, was still observed. 7. A high Q10 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.