Response of thalamocortical neurons to hypoxia: a whole-cell patch-clamp study.
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 degreesC. The predominant feature of the response of TC neurons to hypoxia was an increase in input conductance (DeltaGN = 117 +/- 15%, n = 33) that was accompanied by an inward shift in baseline holding current (IBH) at -65 and -57 mV (DeltaIBH = -45 +/- 6 pA, n = 18, and -25 +/- 8 pA, n = 33, respectively) but not at -40 mV. The hypoxia-induced increase in GN (as well as the shift in IBH) was abolished by procedures that are known to block Ih, i.e., bath application of 4-(N-ethyl-N-phenylamino)-1, 2-dimethyl-6-(methylamino)-pyrimidinium chloride (100-300 microM) (DeltaGN = 5 +/- 13%, n = 11) and CsCl (2-3 mM) (DeltaGN = 16 +/- 16%, n = 5), or low [Na+]o (DeltaGN = 10 +/- 10%, n = 5), whereas bath application of BaCl2 (0.1-2.0 mM) had no significant effect (DeltaGN = 128 +/- 14%, n = 8). The hypoxic response was also abolished in low [Ca+2]o (DeltaGN = 25 +/- 16%, DeltaIBH = -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 (DeltaGN = -3 +/- 15%, DeltaIBH = 10 +/- 5 pA, n = 4). We suggest that a positive shift in the voltage-dependence of Ih and a change in its activation kinetics, which transforms it into a fast activating current, may be responsible for the hypoxia-induced changes in GN and IBH, probably via an increase in Ca+2-dependent transmitter release.
Erdemli
G
G
Physiology Unit, School of Molecular and Medical Biosciences, University of Wales Cardiff, Cardiff, CF1 3US, United Kingdom.
Crunelli
V
V
D000818:Animals; D002118:Calcium; D015687:Cell Hypoxia / Q000502:physiology*; D002540:Cerebral Cortex / Q000473:pathology / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D005829:Geniculate Bodies / Q000473:pathology / Q000502:physiology*; D066298:In Vitro Techniques; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar
D002614:Chelating Agents; D018377:Neurotransmitter Agents; D002118:Calcium