Thermally active TRPV1 tonically drives central spontaneous glutamate release - PubMed (original) (raw)
Temperature strongly augmented spontaneous glutamate release in TRPV1+ compared with TRPV1− second-order NTS neurons. A, Original traces of sEPSCs from representative neurons (left, TRPV1+; right, TRPV1−) show that TRPV1+ neurons typically had higher spontaneous EPSC rates than TRPV1− neurons at each temperature. B, Temperature (upper trace) rapidly and reversibly changed spontaneous EPSC rates in a TRPV1+ (filled circles), but not in a TPRV1− (unfilled circles), neuron. Frequency points are counts >10 s bins, expressed as average frequency. Note that A and B are from same neurons. C, Aggregate summary for temperature responses of seven TRPV1+ (filled circles) and six TRPV1− (unfilled circles) neurons, displayed as means ± SEM. On average (two-way, repeated-measures ANOVA), temperature increased frequency in TRPV1+ (p < 0.001) but not in TRPV1− (_p_ > 0.2). sEPSC amplitudes increased slightly in TRPV1+ (p < 0.001). Decay time constants of sEPSCs (single exponentials, data not shown) declined similarly (p = 0.15) in both TRPV1+ and TRPV1−, decreasing from 3.12 to 1.78 ± 0.09 ms from 25 to 38°C. D, In the absence of action potentials (1 μ
m
TTX), mEPSC frequency increased with temperature. The TRPV1-selective antagonist SB366791 (10 μ
m
, n = 5; left, unfilled squares) significantly decreased mEPSC activity at temperatures >33°C (p < 0.001, two-way repeated-measures ANOVA). In separate TRPV1+ neurons (n = 7; right) temperature sensitivity of mEPSC frequency was reduced (p < 0.001, two-way repeated-measures ANOVA) by reducing bath Ca2+ (right) from control of 2 m
m
(filled circles) to 1 m
m
(unfilled squares) Average values within neurons were binned in 3°C intervals and represented by their midrange. Asterisks mark significant differences. E, In a representative current-clamp example of five TRPV1+ neurons, synaptic potential rates increased substantially with temperature (expanded plots in ovals, right) and action potentials increased accordingly. Two of five neurons inactivated at the highest temperatures.