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

Valentina Comunanza, Emilio Carbone, Andrea Marcantoni, Emanuele Sher, Daniel Ursu

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)709-722
Number of pages14
JournalPflugers Archiv European Journal of Physiology
Volume462
Issue number5
DOIs
Publication statusPublished - Nov 2011

Keywords

  • Capsaicin
  • Nociceptive DRG neurons
  • T-type Cav3.2 channels
  • TRPV1

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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