CELLULAR MECHANISMS UNDERLYING SPONTANEOUS FIRING IN RAT SUPRACHIASMATIC NUCLEUS: INVOLVEMENT OF A SLOWLY INACTIVATING COMPONENT OF SODIUM CURRENT C. M. A. Pennartz, M. A. Bierlaagh and A. M. S. Geurtsen Graduate School Neurosciences Amsterdam, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ, Amsterdam, the Netherlands
APStracts 4:0087N, 1997.
ABSTRACT
Neurons constituting the pacemaker of circadian rhythms, located in the suprachiasmatic nucleus, generate spontaneous firing patterns that change across the day/night cycle. Their average spontaneous firing rate is considered an important functional marker of clock activity, since it is highest during daytime and low at night. In this study we investigated the ionic mechanisms underlying spontaneous firing in acutely prepared slices and dissociated neurons of the suprachiasmatic nucleus. In current clamp mode, spontaneous action potentials were consistently preceded by depolarizing ramps. These ramps were Na+ dependent, sensitive to tetrodotoxin and disappeared upon hyperpolarization. Ramps and associated spikes were not abolished by blockers of the H-current (1 mM cesium) or calcium currents (50 mM nickel or 200 æM cadmium). In voltage-clamped neurons in slices or dissociated neurons, TTX-sensitive and Na+ dependent inward current was observed to activate well below firing threshold (-60 to -50 mV). The low-threshold component of Na+ current inactivated slowly as compared to the fast component that mediates action potentials. However, its inactivation proceeded more rapidly than has been reported for the persistent Na+ current in cortical structures. Persistent Na+ current was generally absent or small in amplitude. The voltage dependence and kinetics of the slowly inactivating component of Na+ current are consistent with the hypothesis that it is partially deinactivated during spike afterhyperpolarizations and contributes significantly to subsequent depolarizing ramps. These observations implicate the slowly inactivating component of Na+ current in ionic mechanisms governing spontaneous firing in suprachiasmatic nucleus neurons.

Received 4 March  1997; accepted in final form 6 June  1997.
APS Manuscript Number J189-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 15 July 1997