Alteration of the conductance of Na+ channels in the nodal membrane of frog nerve by holding potential and tetrodotoxin.

(1) Na+ currents and Na+-current fluctuations were measured in myelinated frog nerve fibres at 15 degrees C during 7.7 ms depolarizations to V = 40, 60 and 80 mV. (2) The conductance gamma of a single Na+ channel and the number No of channels per node were calculated from ensemble average values of the mean Na+ current and the variance of Na+-current fluctuations. (3) For a hyperpolarizing holding potential of VH = -28 mV the mean values of the channel conductance and number were gamma = 9.8 pS and No = 74000. (4) After changing the holding potential to the resting potential (VH = 0) the conductance gamma increased by a factor of 1.37 whereas the number No decreased by a factor of 0.60. (5) Addition of 8 nM tetrodotoxin at a holding potential of VH = -28 mV increased gamma by a factor of 1.55 and reduced No by a factor of 0.25. (6) The increase of the channel conductance at reduced channel numbers suggests negative cooperativity between Na+ channels in the nodal membrane.