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Loeb Medical Research Institute, Ottawa Civic Hospital, University of Ottawa, Ontario, Canada.

1. The electrogenic effects of the Na(+)-K(+)-ATPase in thalamic neurones were investigated by means of intracellular and whole-cell patch-clamp recording techniques in rat medial geniculate body (MGB) maintained in vitro. 2. In twenty-six out of thirty-one neurones recorded intracellularly, application of the Na(+)-K+ pump inhibitor strophanthidin induced two different types of membrane depolarization: a small, reversible depolarization with a peak amplitude of 4 +/- 2.6 mV or a prolonged depolarization of large amplitude (48.6 +/- 9.0 mV) with or without a decrease in apparent membrane resistance. Blockade of glutamate receptors with kynurenic acid or 6-cyano-7-nitroquinoxaline-2,3-dione and (+/-)-2-amino-5-phosphonopentanoic acid did not prevent either type of pump response, but the large depolarization was not seen when the medium contained the sodium channel blocker TTX. 3. Whole-cell patch-clamp recording showed that the small membrane depolarization is mediated by an inward membrane current (39.00 +/- 5.70 pA) that exhibited a weak voltage dependence. An inward current of similar amplitude was also induced in MGB cells when the pipette solution contained nominally zero Na+ or when K+ was temporarily omitted from the extracellular medium. The large membrane depolarization or the corresponding membrane current was not observed in whole-cell conditions. 6. Transient inhibition of the electrogenic Na(+)-K(+)-ATPase consistently led to a change in the mode of synaptic transmission in MGB cells, during which the synaptically evoked burst response was either blocked or converted into a single spike discharge. 7. Taken together, these data suggest that blockade of the electrogenic pump produces a dual membrane effect in mammalian thalamic neurones: a small electrogenic membrane depolarization and a large depolarization response that can be prevented by artificially maintaining the transmembrane ionic gradients. The electrogenic activity of the Na(+)-K(+)-ATPase may play an important role in setting the mode of synaptic transmission in sensory thalamus.