Tetrodotoxin-resistant persistent Na+ current underlying pacemaker potentials of fish gonadotrophin-releasing hormone neurones.

1. Gonadotrophin-releasing hormone (GnRH)-immunoreactive terminal nerve (TN) cells show endogenous regular beating discharges, which may be related to their putative neuromodulator functions. The ionic mechanism underlying the pacemaker potential was studied using intracellular and patch-pipette current clamp recordings from a whole brain in vitro preparation of a small fish brain. 2. The pacemaker potentials were resistant to 1.5-3 microM tetrodotoxin (TTX) and were not affected by Ca2+ channel blockers (amiloride, Ni2+, Co2+, Cd2+) or in Ca(2+)-free solution. In contrast, the pacemaker potentials were readily blocked by substituting tetramethylammonium or choline for Na+ in the perfusing solution, and the resting membrane potential became more hyperpolarized than the control level. 3. The present results suggest that the TTX-resistant persistent Na+ current, INa(slow), supplies the persistent depolarizing drive and plays an important role in the generation of pacemaker potentials in TN GnRH cells.