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 by voltage dependence, kinetics, calcium dependence, and pharmacology. In the presence of Ca channel blockers, the cells heterogeneously expressed transient and sustained outward K+ currents. The transient current was a high-threshold A-current which activated at potentials greater than -30 mV and was blocked by 4-aminopyridine. Some of the sustained current was classified as a delayed rectifier. It demonstrated shallow voltage-dependent inactivation and was blocked by tetraethylammonium. Capsaicin produced large reductions in both transient and sustained currents with an EC50 of 8 microM. Likewise, dendrotoxin partially blocked both currents but with an EC50 of 21 nM. In the absence of Ca channel blockers, a prominent Ca-dependent K+ current was observed. The kinetics of whole-cell potassium currents varied widely among cells, perhaps reflecting the different functional properties of sensory neurons. We also investigated the effects of elevating intracellular cyclic AMP and applying opioids on K+ currents. Membrane-permanent analogs of cyclic AMP and phosphodiesterase inhibitors caused small reductions in voltage-dependent outward current. In contrast, forskolin produced a large reduction in outward current. This response was not solely mediated by cyclic AMP, since large responses were elicited with an inactive congener, 1,9-dideoxyforskolin, but not with the active, water-soluble congener, 7-deacetyl-6-[N-acetylglycyl]-forskolin. Surprisingly, opioids had no effect on resting or voltage-dependent K+ conductances. However, 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+ currents is the principal mechanism for the inhibitory effect of opioids on sensory neurons.
Akins
P T
PT
Department of Cell Biology and Physiology No. 8228, Washington University, St Louis, MO 63110.
McCleskey
E W
EW
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D004546:Elapid Venoms / Q000494:pharmacology; D004594:Electrophysiology; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D009294:Narcotics / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D004546:Elapid Venoms; D009294:Narcotics; D009498:Neurotoxins; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D005576:Colforsin; C020273:dendrotoxin; D015761:4-Aminopyridine; D000242:Cyclic AMP; D002211:Capsaicin