PERMEATION OF NA-ROOT GANGLION NEURONS( THROUGH A DELAYED RECTIFIER K+ CHANNEL IN CHICK DORSAL)

In whole-cell patch clamp recordings from chick dorsal root ganglion n eurons, removal of intracellular K+ resulted in the appearance of a la rge, voltage-dependent inward tail current (I-cat). I-cat was not Ca2 dependent and was not blocked by Cd2+, but was blocked by Ba2+. The r eversal potential for I,, shifted with the Nernst potential for [Na+]. The channel responsible for I-cat had a cation permeability sequence of Na+ >> Li+ >> TMA(+) > NMG(+) (P-x/P-Na = 1:0.33:0.1:0) and was imp ermeable to C1(-). Addition of high intracellular concentrations of K, Cs+, or Rb+ prevented the occurrence of I-cat. Inhibition of I-cat b y intracellular K+ was voltage dependent, with an IC50 that ranged fro m 3.0-8.9 mM at membrane potentials between -50 and -110 mV. This volt age-dependent shift in IC50 (e-fold per 52 mV) is consistent with a si ngle cation binding site similar to 50% of the distance into the membr ane field. I-cat displayed anomolous mole fraction behavior with respe ct to Na+ and K+; I-cat was inhibited by 5 mM extracellular K+ in the presence of 160 mM Na+ and potentiated by equimolar substitution of 80 mM K+ for Na+. The percent inhibition produced by both extracellular and intracellular K+ at 5 mM was identical. Reversal potential measure ments revealed that Kf was 65-105 times more permeant than Na+ through the I-cat channel. I-cat exhibited the same voltage and time dependen ce of inactivation, the same voltage dependence of activation, and the same macroscopic conductance as the delayed rectifier K+ current in t hese neurons. We conclude that I-cat is a Na+ current that passes thro ugh a delayed rectifier K+ channel when intracellular K+ is reduced to below 30 mM. At intracellular K+ concentrations between 1 and 30 mM, P-g/P-Na, remained constant while the conductance at -50 mV varied fro m 80 to O% of maximum. These data suggest that the high selectivity of these channels for K+ over Na+ is due to the inability of Na+ to comp ete with K+ for an intracellular binding site, rather than a barrier t hat excludes Na+ from entry into the channel or a barrier such as a se lectivity filter that prevents Na+ ions from passing through the chann el.