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

The effects of Pb2+ on transient outward currents (TOCs) were investigated on rat dorsal root ganglia (DRG) neurons at postnatal days of 15 similar to 21, using the conventional whale-cell patch-clamp technique. In media-size d (35 similar to 40 mum) neurons and in the presence of 50 mM TEA, TOCs tha t preliminarly included an A-current (I-A) and a D-current (I-D), were clea rly present and dominant. Application of Pb2+ lengthened the initial delay of TOCs and increased the onset-peak time in a concentration-dependent mann er. The amplitudes of initial outward current peak were reduced with increa sing Pb2+ concentrations. The inhibitory effects of Pb2+ on TOCs were rever sible with 80 similar to 90% of current reversed in 2 similar to 10 min at 1 similar to 400 muM Pb2+. 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 Pb2+. 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 muM Pb2+, respectively, indicating that Pb2+ decreased the activation of TOCs. For the normalized steady-state inac tivation 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<plus/minus>2. 98 mV (n=10, P<0.01) at 400 <mu>M Pb2+, respectively. The curves were shift ed to more depolarized voltages by Pb2+, indicating that channels were less likely to be inactivated at higher concentrations of Pb2+ at any given pot ential. The fast (t(t)) and slow (t(s)) decay time-constants were both sign ificantly increased by increasing concentrations of Pb2+ (n=10, P<0.05), in dicating that Pb2+ increased the decay time-course of TOCs. These effects w ere concentration-dependent and partly reversible following washing. Ca2+ m odulated the TOCs gating and might share same binding site with Pb2+, for w hich Ca2+ had very low affinity. In summary, the results demonstrated that Pb2+ was a dose- and voltage-dependent, and reversible blocker of TOCs in r at DRG neurons. After Pb2+ application, normal sensory physiology of DRG ne urons was affected, and these neurons might display aberrant firing propert ies that resulted in abnormal sensations. This variation caused by Pb2+ cou ld underlie the toxical modulation of sensory input to the central nervous system. <(c)> 2001 Elsevier Science BN. All rights reserved.