The Journal of Neurophysiology Vol. 81 No. 1 January 1999, pp. 184-191
Copyright ©1999 The American Physiological Society

Zinc and Flunitrazepam Modulation of GABA-Mediated Currents in Rat Suprachiasmatic Neurons

G. J. Strecker, W. K. Park, and F. E. Dudek

Department of Anatomy and Neurobiology, Colorado State University, Fort Collins, Colorado 80523-1670

Strecker, G. J., W. K. Park, and F. E. Dudek. Zinc and flunitrazepam modulation of GABA-mediated currents in rat suprachiasmatic neurons. J. Neurophysiol. 81: 184-191, 1999. The suprachiasmatic nucleus (SCN) of the hypothalamus is responsible for generating circadian rhythms in mammals, and GABA is the predominant neurotransmitter in the SCN. Properties of -aminobutyric acid-A (GABA_A) responses in SCN neurons were examined in acutely prepared hypothalamic slices from 3- to 8-wk-old rats with the use of whole cell voltage-clamp techniques. Zn²⁺ reduced the amplitude of GABA_A-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in a concentration-dependent manner ranging from a reduction of control amplitude to 88% at 10 µM to 27% at 1,000 µM. Zn²⁺ reduced IPSC amplitude to a similar degree in the presence of tetrodotoxin and also significantly reduced the amplitude of currents evoked by application of exogenous GABA (100 µM, pressure applied). Zn²⁺ increased the frequency of IPSCs at lower concentrations and decreased it at higher ones. Flunitrazepam (100 nM) usually failed to potentiate the amplitude of sIPSCs, but prolonged sIPSC kinetics. Two exponential components were normally resolved in the sIPSC decay constants, and flunitrazepam significantly increased those two components. Thus flunitrazepam increased the duration of sIPSCs and potentiated the amplitude of currents evoked by pressure application of GABA. Zn²⁺ and benzodiazepine each modulated the effect of GABA in nearly all cells, suggesting that most SCN neurons have a similar GABA_A receptor subunit composition in this respect. Zn²⁺ also affected sIPSC frequency, which suggests that Zn²⁺ increased neuronal firing rate at lower concentrations. These results begin to define the cellular roles that these GABA_A receptor modulators might play in circadian regulation.

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