It has been documented that nodose neurons express TTX-sensitive (TTX-S) and TTX-resistant (TTX-R) Na+ channels. However, wheteher nodose neurons functionally express persistent TTX-R Na+ currents has not been reported. The present study first demonstrated persistent TTX-R Na+ channel activities in 7/19 C-type nodose neurons in the presence of PGE(2) using whole-cell patch. Voltage-dependent property showed that persistent TTX-R Na+ currents were activated at near -60 mV and channels were maintained open. The average peak was approximately 300-500 pA. The mid-point of activation exhibited a greater shift to a more hyperpolarized potential in the neurons co-expressing TTX-R and persistent TTX-R Na+ currents than those expressing TTX-R only. This effect of PGE(2), was also mimicked by Forskolin. The fact that persistent TTX-R Na+ currents were only activated by PGE(2) suggested that the modulatory effects of PGE(2) on persistent TTX-R Na+ currents are crucial in PGE(2)-mediated neuronal excitability, and may have a great impact on specifically physiological significance. (c) 2007 Elsevier Inc. All rights reserved.