The effects of lead on transient outward currents of acutely dissociated rat dorsal root ganglia

Abstract

The effects of Pb 2+ on transient outward currents (TOCs) were investigated on rat dorsal root ganglia (DRG) neurons at postnatal days of 15∼21, using the conventional whole-cell patch-clamp technique. In media-sized (35∼40 μm) neurons and in the presence of 50 mM TEA, TOCs that preliminarly included an A-current ( I A) and a D-current ( I D), were clearly present and dominant. Application of Pb 2+ lengthened the initial delay of TOCs and increased the onset-peak time in a concentration-dependent manner. The amplitudes of initial outward current peak were reduced with increasing Pb 2+ concentrations. The inhibitory effects of Pb 2+ on TOCs were reversible with 80∼90% of current reversed in 2∼10 min at 1∼400 μM Pb 2+. For the normalized activation curves fitted by a single Boltzmann equation under each condition, there was a shift to more depolarized voltages with increasing concentrations of Pb 2+. The V 1/2 and the slope factor ( k) increased from 12.76±1.49 mV and 15.31±1.66 mV ( n=10) under control condition to 39.91±5.44 mV ( n=10, P<0.01) and 21.39±3.13 mV ( n=10, P<0.05) at 400 μM Pb 2+, respectively, indicating that Pb 2+ decreased the activation of TOCs. For the normalized steady-state inactivation curves, the V 1/2 and the k increased from −92.31±2.72 and 8.59±1.36 mV ( n=10) to −55.65±3.67 ( n=10, P<0.01) and 23.02±2.98 mV ( n=10, P<0.01) at 400 μM Pb 2+, respectively. The curves were shifted to more depolarized voltages by Pb 2+, indicating that channels were less likely to be inactivated at higher concentrations of Pb 2+ at any given potential. The fast ( t f) and slow ( t s) decay time-constants were both significantly increased by increasing concentrations of Pb 2+ ( n=10, P<0.05), indicating that Pb 2+ increased the decay time-course of TOCs. These effects were concentration-dependent and partly reversible following washing. Ca 2+ modulated the TOCs gating and might share same binding site with Pb 2+, for which Ca 2+ had very low affinity. In summary, the results demonstrated that Pb 2+ was a dose- and voltage-dependent, and reversible blocker of TOCs in rat DRG neurons. After Pb 2+ application, normal sensory physiology of DRG neurons was affected, and these neurons might display aberrant firing properties that resulted in abnormal sensations. This variation caused by Pb 2+ could underlie the toxical modulation of sensory input to the central nervous system.