Differential effects of tetrodotoxin (TTX) and high external K+ on A and C fibre compound action potential peaks in frog sciatic nerve

Monophasic compound action potentials were recorded from Rana sciatic nerves. Three distinct peaks were observed and designated A alpha, A delta and C. All peaks were abolished by replacement of the external medium with Na+-free solution. However, the C peak alone was unaffected by external application of 1 mu M tetrodotoxin (TTX), both A peaks were completely suppressed. The C peak was also the most resistant to chronic depolarization caused by increased external K+. K+ (17.6 mM) solution reduced peak areas to 5 +/- 4, 27 +/- 11 and 63 +/- 14% of control for A alpha, A delta and C components. The C peak was therefore Na+-dependent, TTX-resistant and K+-depolarization resistant. These attributes are similar to those described for somatal TTX-resistant Na+ channels in other species. But, application of 1 mu M TTX to a K+-depolarized nerve caused a further reduction in C peak area, suggestive of a voltage-dependent block by TTX similar to that reported for cardiac muscle Na+ channels.