Time- and frequency-dependent effects of potassium channel blockers on large and medium diameter optic tract axons

Compound action potential recording techniques were used to investigate the time- and frequency-dependent effects of 4-aminopyridine (4-AP) and tetraethylammonium (TEA) on large diameter, fast conducting (t1) and medium diameter, middle conducting (t2) optic tract axons in anesthetized hooded rats. Single-pulse studies show 4-AP causes a rapid decrease in t1 and t2 response amplitude with larger decreases and longer lasting effects in t2 axons. In both axons, 4-AP leads to waveform broadening which is accounted for by increases in fall time since rise time and conduction velocity are unaffected by 4-AP. Strength-duration curves reveal 4-AP increases rheobase and decreases chronaxie in both axons with larger increases occurring in t1. T1, but not t2, axons also display some TEA-sensitivity. The absolute and relative refractory periods, determined with paired-pulse recovery functions, are increased by 4-AP to a greater degree in t1 than t2 axons. These axons, however, display equal sensitivity to TEA. In contrast, 4-AP and TEA decrease frequency following in both axons with larger effects observed in t2. Based on our data, and that of others, we speculate that t1 axons exhibit 4-AP and TEA sensitivity at nodal/paranodal regions and not at internodal regions, while t2 axons exhibit 4-AP sensitivity at nodal/paranodal and internodal regions and TEA sensitivity only at internodal regions of the axolemma. The possible relevance of these findings to the distribution of 4-AP- and TEA-sensitive potassium channels on t1 and t2 axons and the coding of visual spatial and temporal information remains to be determined.