title: Calcium-dependent inhibition of T-type calcium channels by TRPV1 activation in rat sensory neurons.
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).
authors: Department of Neuroscience, NIS Center, CNISM Research Unit, 10125, Torino, Italy.
authors: Valentina
authors: V
authors: Comunanza
authors: Emilio
authors: E
authors: Carbone
authors: Andrea
authors: A
authors: Marcantoni
authors: Emanuele
authors: E
authors: Sher
authors: Daniel
authors: D
authors: Ursu
mesh_terms: D000818:Animals; D001464:Barium / Q000494:pharmacology; D019703:Calcineurin / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D020747:Calcium Channels, T-Type / Q000187:drug effects*; D002147:Calmodulin / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000502:physiology; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000502:physiology; D050916:TRPV Cation Channels / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D020747:Calcium Channels, T-Type; D002147:Calmodulin; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D001464:Barium; D004533:Egtazic Acid; D019703:Calcineurin; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002211:Capsaicin; D002118:Calcium