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 Iheat 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 Iheat exhibited a strong temperature sensitivity (temperature coefficient over a 10 °C temperature range ( Q 10 ) = 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 Q 10 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 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 Ca 2+ , Q 10 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 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.