The effect of capsaicin on voltage‐gated calcium currents and calcium signals in cultured dorsal root ganglion cells

Abstract

1 The effects of capsaicin on voltage-gated Ca²⁺ currents (I_Ca), and intracellular Ca²⁺ concentrations ([Ca²⁺]_i) in cultured dorsal root ganglion (DRG) neurones of the rat were examined in vitro by use of combined patch clamp-microfluorometric recordings. 2 Under voltage-clamp conditions, capsaicin (0.1–10 μm) caused a concentration-dependent decrease in the magnitude of the I_Ca, an elevation in the holding current (I_h) and a concomitant rise in the [Ca²⁺]_i in most cells examined. Repeated application of capsaicin produced marked desensitization. 3 Some decrease in the I_Ca produced by capsaicin was also observed when the rise in [Ca²⁺]_i was buffered with EGTA or BAPTA and when Ba²⁺ was used as the charge carrier; under these conditions the desensitization previously observed was smaller. 4 The decrement in voltage-gated current was smaller in Ba²⁺ containing solutions than in Ca²⁺ containing solutions suggesting that the capsaicin-induced influx of Ca²⁺ partially mediated the observed decrease in the voltage-gated current. In cells which showed a marked response to capsaicin an outward (positive) current was sometimes observed upon depolarization from −80 to 0mV. This effect was consistent with an outward movement of cations through the capsaicin conductance pathway which may also account, in part, for the apparent reduction in I_Ca by capsaicin. 5 The effects of capsaicin under voltage-clamp conditions were prevented by ruthenium red (1 μm). 6 Under current clamp conditions, capsaicin depolarized and caused a rise in [Ca²⁺]_i in the majority of DRG cells examined. Both of these effects could be prevented by ruthenium red (500 nm). 7 It is concluded that capsaicin reduces the I_Ca of rat DRG neurones primarily by indirect mechanisms.