Characterization of TTX-resistant persistent Na+ current underlying pacemaker potentials of fish gonadotropin-releasing hormone (GnRH) neurons.

1. Endogenous pacemaker activities are important for the putative neuromodulator functions of the gonadotropin-releasing hormone (GnRH)-immunoreactive terminal nerve (TN) cells. Previously we have shown by current-clamp analysis that a tetrodotoxin (TTX)-resistant persistent Na+ current, INa(slow), plays an important role in the generation of pacemaker potentials of TN-GnRH cells. The present study investigates electrophysiological characteristics of INa(slow) by using the whole cell patch-clamp technique in in vitro whole-brain preparation of a small fish brain. 2. TN-GnRH cells lie immediately beneath the ventral meningeal membrane; the cells could thus be exposed and visualized by gently removing the meningeal membrane. INa(slow) currents were isolated pharmacologically by blocking K+ currents, Ca2+ currents, and conventional fast Na+ currents. 3. INa(slow) was characterized by resistance to TTX blockade, dependence on external Na+, slow activation, very slow and little inactivation, and wide overlap of activation and inactivation curves near the resting potential. These characteristics are distinct from those of conventional fast Na+ current, and are relevant for the generation of persistent inward currents necessary for the pacemaker activity of TN-GnRH cells.