Functional Roles of the Sodium Pump in Clock Neuorns of the Rat Suprachiasmatic Nucleus

  • Huang, Rong-Chi (PI)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

The central circadian clock resides in the hypothalamic suprachiasmatic nucleus (SCN) to coordinate the peripheral oscillators in controlling biochemical, physiological, and behavioral rhythms in mammals. These clock neurones vary their activity across the time of day, exhibiting circadian rhythms in spontaneous firing rate and in intracellular Ca2+ concentrations. They also exhibit metabolic rhythms in glucose uptake and ATP contents. The daily variation in firing activity, which would likely produce varying degrees of dissipation of Na+ and K+ gradients, suggests that the pumping activity of the Na+/K+-ATPase might also be altered accordingly to meet the daily fluctuations in the ionic environments. Indeed, we demonstrate that SCN neurons exhibit a diurnal rhythm in pump activity and firing activity in reduced SCN preparations, both being higher during the day than at night. In particular, the in-phase oscillation of sodium pump activity with firing activity is accordant with the metabolic roles of this enzyme in maintaining the Na+ and K+ gradients, and might thus provide a way to couple metabolic rhythm to firing rhythm in clock neurons. Although an exact relationship between the firing and metabolic rhythms is not known, the pump activity appears to be intimately tied to the firing activity. On the one hand, the firing rate of SCN neurons is potently regulated by pump activity, as demonstrated by the marked increase in spontaneous firing in response to the cardiac steroid strophanthidin or the application of K+-free solution to block the sodium pump. On the other hand, the sodium pump also appeared to be regulated by the firing activity, as suggested by the prolonged rebound inhibition of firing on return from zero K+ to normal K+. The suggestion comes from the expectation that an accumulation of intracellular Na+, brought about by the blockade of the sodium pump with zero K+, should enhance pump activity to inhibit spontaneous firing on return to normal K+. In other words, intracellular Na+, via its action on the sodium pump, appears to regulate the spontaneous firing rate of SCN neurons. This raises an interesting question as to the sources for Na+ influx that activates the sodium pump. Our preliminary results indicate that Na+ influx independent of TTX-sensitive Na+-channels is able to activate the sodium pump. In this two years project, we will test the hypothesis that intracellular Na+, via the sodium pump, regulates spontaneous firing activity in SCN neurons and then go on to determine the sources for Na+ influx that activates the sodium pump. Experiments will be done with neurons in reduced SCN preparations. The firing rate, membrane potentials, and membrane currents will be recorded with the cell-attached and whole-cell current-clamped and voltage-clamped techniques. We will determine that intracellular accumulation of Na+ activate the sodium pump to suppress neuronal firing. Furthermore, we will also determine the nature of sodium leak and its functional couplings to the sodium pump. Completion of this project should advance our understanding as to the functional roles of sodium pump in the central clock neurons.

Project IDs

Project ID:PC9706-0486
External Project ID:NSC96-2320-B182-028-MY2
StatusFinished
Effective start/end date01/08/0831/07/09

Keywords

  • suprachiasmatic nucleus
  • spontaneous firing rate
  • Na+/K+-ATPase
  • sodium pump,sodium leak
  • whole-cell recordings

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