Riluzole-sensitive slowly inactivating sodium current in rat suprachiasmatic nucleus neurons.
The persistent (i.e., slowly inactivating) fraction of the Na current (I(Na,P)) regulates excitability of CNS neurons. In isolated rat suprachiasmatic nucleus (SCN) neurons with a ramp-type voltage-clamp protocol, we have studied the properties of a robust current that has the general properties of I(Na,P) but exhibits a slow inactivation (I(Na,S)). The time dependence of the development of the inactivation was also studied by clamping of the membrane potential at different levels: time constants ranging from approximately 50 to approximately 700 ms, depending on the voltage level, were revealed. The I(Na,S) (50-150 pA) was present in both spontaneously active and silent neurons. The neurons exhibited I(Na,S) without visible rundown during approximately 1-h recordings. I(Na,S) had a threshold between -65 and -60 mV and was maximal at about -45 mV. Tetrodotoxin (TTX; 1 microM) completely and reversibly blocked I(Na,S). Riluzole, an effective blocker of I(Na,P), inhibited reversibly I(Na,S) with an EC(50) of 1-2 microM. Microapplication of 10 microM riluzole during either extracellular or intracellular recording suppressed spontaneous activity in isolated SCN neurons. In the slice preparation, bath application of 20 microM riluzole resulted in decreased firing rate or complete suppression of spontaneous activity in some neurons (9/14) but had no effect on other neurons (5/14). In riluzole-resistant neurons in cell-attached experiments, low-amplitude current spikes were present in 1 microM TTX. We concluded that I(Na,S) is ubiquitously expressed by all SCN neurons and that this current is a necessary but not sufficient depolarizing component of the mechanism for spontaneous firing.
Department of Biomedical Sciences, Anatomy and Neurobiology Section, Colorado State University, Fort Collins, Colorado 80523, USA.
Nikolai I
NI
Kononenko
Li-Rong
LR
Shao
F Edward
FE
Dudek
D000818:Animals; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019782:Riluzole / Q000494:pharmacology*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000502:physiology*; D013493:Suprachiasmatic Nucleus / Q000187:drug effects* / Q000502:physiology
D026941:Sodium Channel Blockers; D015222:Sodium Channels; D019782:Riluzole