Inhibition of calcium currents in cultured rat dorsal root ganglion neurones by (−)‐baclofen

Abstract

Voltage‐dependent inward calcium currents (ICa) activated in cultured rat dorsal root ganglion neurones were reversibly reduced in a dose‐dependent manner by (−)‐baclofen (10 μM to 100 μM). Baclofen (100 μM) reduced the calcium‐dependent slow outward potassium current (IK(Ca)). This current was abolished in calcium‐free medium and by 300 μM cadmium chloride. The action of baclofen on IK(Ca) was reduced when the calcium concentration in the medium was increased from 5 mM to 30 mM. The calcium independent fast transient voltage‐dependent outward current (IK(Vt)) was also reduced by baclofen; this effect remained present when Ca2+‐free medium was used to prevent contamination by IK(Ca). 4‐Aminopyridine (500 μM) reduced IK(Vt) and induced a small increase in ICa. The action of baclofen on ICa was partially antagonized by 4‐aminopyridine. GABAB receptor‐mediated inhibition of ICa in cultured rat dorsal root ganglion neurones involves a direct mechanism rather than resulting indirectly from an increase in the residual outward potassium currents activated by depolarization. The reduction in ICa by baclofen was variable and dependent on the amplitude of control ICa, larger currents being more resistant to the baclofen‐induced inhibition. 1986 British Pharmacological Society