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The Journal of Neuroscience, July 15, 1998, 18(14):5212-5224

Response of Thalamocortical Neurons to Hypoxia: A Whole-Cell Patch-Clamp Study

Gül Erdemli and Vincenzo Crunelli

Physiology Unit, School of Molecular and Medical Biosciences, University of Wales Cardiff, Cardiff, CF1 3US, United Kingdom

The effect of hypoxia (3-4 min of 95% N₂, 5% CO₂) on thalamocortical (TC) neurons was investigated using the whole-cell patch-clamp technique in rat dorsal lateral geniculate nucleus slices kept submerged at 32°C. The predominant feature of the response of TC neurons to hypoxia was an increase in input conductance (G_N = 117 ± 15%, n = 33) that was accompanied by an inward shift in baseline holding current (I_BH) at 65 and 57 mV (I_BH = 45 ± 6 pA, n = 18, and 25 ± 8 pA, n = 33, respectively) but not at 40 mV. The hypoxia-induced increase in G_N (as well as the shift in I_BH) was abolished by procedures that are known to block I_h, i.e., bath application of 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)-pyrimidinium chloride (100-300 µM) (G_N = 5 ± 13%, n = 11) and CsCl (2-3 mM) (G_N = 16 ± 16%, n = 5), or low [Na⁺]_o (G_N = 10 ± 10%, n = 5), whereas bath application of BaCl₂ (0.1-2.0 mM) had no significant effect (G_N = 128 ± 14%, n = 8). The hypoxic response was also abolished in low [Ca⁺²]_o (G_N = 25 ± 16%, I_BH = 6 ± 8 pA, n = 13), but was unaffected by recording with electrodes containing EGTA (10 mM), BAPTA (10-30 mM), Cs⁺, or Cl, as well as in the presence of external tetraethylammonium and 4-aminopyridine. Furthermore, preincubation of the slices with botulinum toxin A (100 nM), which is known to reduce Ca²⁺-dependent transmitter release, blocked the hypoxic response (G_N = 3 ± 15%, I_BH = 10 ± 5 pA, n = 4).

We suggest that a positive shift in the voltage-dependence of I_h and a change in its activation kinetics, which transforms it into a fast activating current, may be responsible for the hypoxia-induced changes in G_N and I_BH, probably via an increase in Ca⁺²-dependent transmitter release.

Key words: hypoxia; I_h; inward rectification; cesium; ZD 7288; dorsal lateral geniculate nucleus; botulinum toxin; transmitter release

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18145212-13$05.00/0

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