CHARACTERIZATION OF POTASSIUM CURRENTS IN ADULT-RAT SENSORY NEURONS AND MODULATION BY OPIOIDS AND CYCLIC-AMP

Using the whole-cell patch-clamp technique on acutely dissociated and cultured adult rat sensory neurons, we characterized the K+ currents b y voltage dependence, kinetics, calcium dependence, and pharmacology. In the presence of Ca channel blockers, the cells heterogeneously expr essed transient and sustained outward K+ currents. The transient curre nt was a high-threshold A-current which activated at potentials greate r than -30 mV and was blocked by 4-aminopyridine. Some of the sustaine d current was classified as a delayed rectifier. It demonstrated shall ow voltage-dependent inactivation and was blocked by tetraethylammoniu m. Capsaicin produced large reductions in both transient and sustained currents with an EC50 of 8 muM. Likewise, dendrotoxin partially block ed both currents but with an EC50 of 21 nM. In the absence of Ca chann el blockers, a prominent Ca-dependent K+ current was observed. The kin etics of whole-cell potassium currents varied widely among cells, perh aps reflecting the different functional properties of sensory neurons. We also investigated the effects of elevating intracellular cyclic AM P and applying opioids on K+ currents. Membrane-permanent analogs of c yclic AMP and phosphodiesterase inhibitors caused small reductions in voltage-dependent outward current. In contrast, forskolin produced a l arge reduction in outward current. This response was not solely mediat ed by cyclic AMP, since large responses were elicited with an inactive congener, 1,9-dideoxyforskolin, but not with the active, water-solubl e congener, 7-deacetyl-6-[N-acetylglycyl]-forskolin. Surprisingly, opi oids had no effect on resting or voltage-dependent K+ conductances. Ho wever, opioid inhibition of Ca2+ currents and Ca-dependent K+ currents was observed. The failure to demonstrate opioid modulation of resting or voltage dependent K+ currents suggests that modulation of Ca2+ cur rents is the principal mechanism for the inhibitory effect of opioids on sensory neurons.