Abstract
We studied the inhibitory effects of transient receptor potential vanilloid-1 (TRPV1) activation by capsaicin on low-voltage-activated (LVA, T-type) Ca 2+ channel and high-voltage-activated (HVA; L, N, P/Q, R) currents in rat DRG sensory neurons, as a potential mechanism underlying capsaicin-induced analgesia. T-type and HVA currents were elicited in whole-cell clamped DRG neurons using ramp commands applied before and after 30-s exposures to 1 μM capsaicin. T-type currents were estimated at the first peak of the I-V characteristics and HVA at the second peak, occurring at more positive potentials. Small and medium-sized DRG neurons responded to capsaicin producing transient inward currents of variable amplitudes, mainly carried by Ca 2+. In those cells responding to capsaicin with a large Ca 2+ influx (59% of the total), a marked inhibition of both T-type and HVA Ca 2+ currents was observed. The percentage of T-type and HVA channel inhibition was prevented by replacing Ca 2+ with Ba 2+ during capsaicin application or applying high doses of intracellular BAPTA (20 mM), suggesting that TRPV1-mediated inhibition of T-type and HVA channels is Ca 2+-dependent and likely confined to membrane nano-microdomains. Our data are consistent with the idea that TRPV1-induced analgesia may derive from indirect inhibition of both T-type and HVA channels which, in turn, would reduce the threshold of nociceptive signals generation (T-type channel inhibition) and nociceptive synaptic transmission (HVA-channels inhibition).
| Original language | English |
|---|---|
| Pages (from-to) | 709-722 |
| Number of pages | 14 |
| Journal | Pflugers Archiv European Journal of Physiology |
| Volume | 462 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Nov 2011 |
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Keywords
- Capsaicin
- Nociceptive DRG neurons
- T-type Cav3.2 channels
- TRPV1
ASJC Scopus subject areas
- Physiology
- Clinical Biochemistry
- Physiology (medical)
Cite this
Calcium-dependent inhibition of T-type calcium channels by TRPV1 activation in rat sensory neurons. / Comunanza, Valentina; Carbone, Emilio; Marcantoni, Andrea; Sher, Emanuele; Ursu, Daniel.
In: Pflugers Archiv European Journal of Physiology, Vol. 462, No. 5, 11.2011, p. 709-722.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Calcium-dependent inhibition of T-type calcium channels by TRPV1 activation in rat sensory neurons
AU - Comunanza, Valentina
AU - Carbone, Emilio
AU - Marcantoni, Andrea
AU - Sher, Emanuele
AU - Ursu, Daniel
PY - 2011/11
Y1 - 2011/11
N2 - We studied the inhibitory effects of transient receptor potential vanilloid-1 (TRPV1) activation by capsaicin on low-voltage-activated (LVA, T-type) Ca 2+ channel and high-voltage-activated (HVA; L, N, P/Q, R) currents in rat DRG sensory neurons, as a potential mechanism underlying capsaicin-induced analgesia. T-type and HVA currents were elicited in whole-cell clamped DRG neurons using ramp commands applied before and after 30-s exposures to 1 μM capsaicin. T-type currents were estimated at the first peak of the I-V characteristics and HVA at the second peak, occurring at more positive potentials. Small and medium-sized DRG neurons responded to capsaicin producing transient inward currents of variable amplitudes, mainly carried by Ca 2+. In those cells responding to capsaicin with a large Ca 2+ influx (59% of the total), a marked inhibition of both T-type and HVA Ca 2+ currents was observed. The percentage of T-type and HVA channel inhibition was prevented by replacing Ca 2+ with Ba 2+ during capsaicin application or applying high doses of intracellular BAPTA (20 mM), suggesting that TRPV1-mediated inhibition of T-type and HVA channels is Ca 2+-dependent and likely confined to membrane nano-microdomains. Our data are consistent with the idea that TRPV1-induced analgesia may derive from indirect inhibition of both T-type and HVA channels which, in turn, would reduce the threshold of nociceptive signals generation (T-type channel inhibition) and nociceptive synaptic transmission (HVA-channels inhibition).
AB - We studied the inhibitory effects of transient receptor potential vanilloid-1 (TRPV1) activation by capsaicin on low-voltage-activated (LVA, T-type) Ca 2+ channel and high-voltage-activated (HVA; L, N, P/Q, R) currents in rat DRG sensory neurons, as a potential mechanism underlying capsaicin-induced analgesia. T-type and HVA currents were elicited in whole-cell clamped DRG neurons using ramp commands applied before and after 30-s exposures to 1 μM capsaicin. T-type currents were estimated at the first peak of the I-V characteristics and HVA at the second peak, occurring at more positive potentials. Small and medium-sized DRG neurons responded to capsaicin producing transient inward currents of variable amplitudes, mainly carried by Ca 2+. In those cells responding to capsaicin with a large Ca 2+ influx (59% of the total), a marked inhibition of both T-type and HVA Ca 2+ currents was observed. The percentage of T-type and HVA channel inhibition was prevented by replacing Ca 2+ with Ba 2+ during capsaicin application or applying high doses of intracellular BAPTA (20 mM), suggesting that TRPV1-mediated inhibition of T-type and HVA channels is Ca 2+-dependent and likely confined to membrane nano-microdomains. Our data are consistent with the idea that TRPV1-induced analgesia may derive from indirect inhibition of both T-type and HVA channels which, in turn, would reduce the threshold of nociceptive signals generation (T-type channel inhibition) and nociceptive synaptic transmission (HVA-channels inhibition).
KW - Capsaicin
KW - Nociceptive DRG neurons
KW - T-type Cav3.2 channels
KW - TRPV1
UR - http://www.scopus.com/inward/record.url?scp=80054757483&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80054757483&partnerID=8YFLogxK
U2 - 10.1007/s00424-011-1023-5
DO - 10.1007/s00424-011-1023-5
M3 - Article
C2 - 21904821
AN - SCOPUS:80054757483
VL - 462
SP - 709
EP - 722
JO - Pflugers Archiv European Journal of Physiology
JF - Pflugers Archiv European Journal of Physiology
SN - 0031-6768
IS - 5
ER -