Analgesic transient receptor potential vanilloid‐1‐active compounds inhibit native and recombinant T‐type calcium channels

BACKGROUND AND PURPOSE: T‐type calcium (Ca(v)3) and transient receptor potential vanilloid‐1 (TRPV1) channels play central roles in the control of excitability in the peripheral nervous system and are regarded as potential therapeutic pain targets. Modulators that either activate or inhibit TRPV1‐mediated currents display analgesic properties in various pain models despite opposing effects on their connate target, TRPV1. We explored the effects of TRPV1‐active compounds on Ca(v)3‐mediated currents. EXPERIMENTAL APPROACH: Whole‐cell patch clamp recordings were used to examine the effects of TRPV1‐active compounds on rat dorsal root ganglion low voltage‐activated calcium currents and recombinant Ca(v)3 isoforms in expression systems. KEY RESULTS: The classical TRPV1 agonist capsaicin as well as TRPV1 antagonists A‐889425, BCTC, and capsazepine directly inhibited Ca(v)3 channels. These compounds altered the voltage‐dependence of activation and inactivation of Ca(v)3 channels and delayed their recovery from inactivation, leading to a concomitant decrease in T‐type current availability. The TRPV1 antagonist capsazepine potently inhibited Ca(v)3.1 and 3.2 channels (K (D)