It has been shown that desensitization of the native capsaicin receptor VR-1 in rat dorsal root ganglion (DRG) neurones is strongly dependent on intracellular calcium concentration, with desensitization being nearly absent when Ca²⁺ is buffered to very low levels (Cholewinski et al. 1993; Koplas et al. 1997). Previous studies have been made at room temperature; here we show that at normal mammalian body temperature, native VR-1 undergoes pronounced desensitization during capsaicin application, even under low Ca²⁺ conditions.

DRG neurones were cultured from adult rats (humanely killed by CO₂ inhalation and decapitation). After 1-3 days, cells were clamped at -80 mV in the whole-cell configuration, using Ca²⁺-free bath solution containing 1 mM EGTA and a Cs⁺-based pipette solution containing 10 mM BAPTA. Temperature was controlled by a Peltier-based system (Reid et al. 2001). Capsaicin was applied at a concentration of 500 nM, and was used only once in each dish of cells.

At cold (15 °C) and room temperature (25 °C) desensitization was nearly absent, but at body temperature (37 °C), the capsaicin-induced current reached a maximum after 20.3 ± 3.8 s (n = 6, mean ± S.E.M.) followed by a rapid desensitization with a time constant of 25.5 ± 3.4 s (n = 6). Within 30 s after the peak, the current had decreased by 59.9 ± 4.3 % (n = 6). Increasing the temperature to 45 °C, just above the thermal threshold of VR-1 in the absence of capsaicin, the time to peak decreased to 10.8 ± 1.0 s (n = 5, P = 0.027, Student’s unpaired t test) and the desensitization time constant was faster than at body temperature (14.4 ± 3.4 s, n = 5, P = 0.0069).

We conclude that when Ca²⁺ is buffered to very low levels, acute desensitization of native VR-1 is weak at low temperature, including room temperature. However, at body temperature (37 °C) and at elevated temperature (45 °C), acute desensitization is strong and rapid, even when extracellular and intracellular [Ca²⁺] are very low.

Financial support was from the Romanian Ministry of Education (World Bank grants C-326, B-50), NATO and the Volkswagen Foundation.