We studied the inhibitory effects of transient receptor potential vanilloid-1 (TRPV1) activation by capsaicin on low-voltage-activated (LVA, T-type) Ca2+ channel and highvoltage- 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 Ca2+. In those cells responding to capsaicin with a large Ca2+ influx (59% of the total), a marked inhibition of both T-type and HVA Ca2+ currents was observed. The percentage of T-type and HVA channel inhibition was prevented by replacing Ca2+ with Ba2+ during capsaicin application or applying high doses of intracellular BAPTA (20 mM), suggesting that TRPV1- mediated inhibition of T-type and HVA channels is Ca2+- dependent and likely confined to membrane nanomicrodomains. 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).

Calcium-dependent inhibition of T-type calcium channels by TRPV1 activation in rat sensory neurons

COMUNANZA, Valentina;CARBONE, Emilio;MARCANTONI, Andrea;
2011

Abstract

We studied the inhibitory effects of transient receptor potential vanilloid-1 (TRPV1) activation by capsaicin on low-voltage-activated (LVA, T-type) Ca2+ channel and highvoltage- 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 Ca2+. In those cells responding to capsaicin with a large Ca2+ influx (59% of the total), a marked inhibition of both T-type and HVA Ca2+ currents was observed. The percentage of T-type and HVA channel inhibition was prevented by replacing Ca2+ with Ba2+ during capsaicin application or applying high doses of intracellular BAPTA (20 mM), suggesting that TRPV1- mediated inhibition of T-type and HVA channels is Ca2+- dependent and likely confined to membrane nanomicrodomains. 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).
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http://www.springerlink.com/content/e01w205631q21522/
canali TRPV1; canali del calcio di tipo T; neuroni sensoriali; dolore iperalgesico
Valentina Comunanza; Emilio Carbone; Andrea Marcantoni; Emanuele Sher; Daniel Ursu
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/90808
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