Interaction between amino acid induced and K+-induced depolarization of primary afferents in the bullfrog spinal cord.

In view of the possible contribution of both gamma-aminobutyric acid (GABA) and K+ to primary afferent depolarization (PAD) it was of interest to study the way in which depolarizations caused by administration of these agents combine at the primary afferent membrane. GABA (and glutamate) depolarizations of bullfrog afferents were found to be reduced if they were superimposed on ongoing K+-induced depolarizations. The extent of reduction was greater with K+ depolarizations of increasing size. The contribution of GABA to PAD should therefore be greatest when extracellular K+ is low, such as during single volleys or low frequency afferent activity. The effect of temporal order of administration on the summation of amino acid and K+ responses was tested by reversing the order of their application. GABA could not be used in this test because GABA depolarizations rapidly desensitize. However, when K+ depolarization was superimposed on maintained glutamate depolarization, the total depolarization was equal to the sum of depolarizations observed when glutamate and K+ were given alone (linear summation). Therefore, the temporal order of administration of amino acid and K+ affects the size of the total depolarization. No evidence was found for a superadditive effect when amino acid and K+ were applied together.