Similar propagation of SD and hypoxic SD-like depolarization in rat hippocampus recorded optically and electrically.
Neuron membrane changes and ion redistribution during normoxic spreading depression (SD) induced, for example, by potassium injection, closely resemble those that occur during hypoxic SD-like depolarization (HSD) induced by oxygen withdrawal, but the degree to which the two phenomena are related is controversial. We used extracellular electrical recording and imaging of intrinsic optical signals in hippocampal tissue slices to compare 1) initiation and spread of these two phenomena and 2) the effects of putative gap junction blocking agents, heptanol and octanol. Both events arose focally, after which a clear advancing wave front of increased reflectance and DC shift spread along the CA1 stratum radiatum and s. oriens. The rate of spread was similar: conduction velocity of normoxic SD was 8.73 +/- 0.92 mm/min (mean +/- SE) measured electrically and 5.84 +/- 0.63 mm/min measured optically, whereas HSD showed values of 7.22 +/- 1.60 mm/min (electrical) and 6.79 +/- 0.42 mm/min (optical). When initiated in CA1, normoxic SD consistently failed to enter the CA3 region (7/7 slices) and could not be initiated by direct KC1 injection in the CA3 region (n = 3). Likewise, the hypoxic SD-like optical signal showed onset in the CA1 region and halted at the CA1/CA3 boundary (9/9 slices), but in some (4/9) slices the dentate gyrus region showed a separate onset of signal changes. Microinjection into CA1 stratum radiatum of octanol (1 mM), which when bath applied arrests the spread of normoxic SD, created a small focus that appeared to be protected from hypoxic depolarization. However, bath application of heptanol (3 mM) or octanol (2 mM) did not prevent the spread of HSD, although the onset was delayed. This suggests that, although gap junctions may be essential for the spread of normoxic SD, they may play a less important role in the spread of HSD.
Aitken
P G
PG
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, USA.
Tombaugh
G C
GC
Turner
D A
DA
Somjen
G G
GG
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology*; D019850:Heptanol / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000503:physiopathology*; D002534:Hypoxia, Brain / Q000503:physiopathology*; D007091:Image Processing, Computer-Assisted; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D000442:Octanols / Q000494:pharmacology; D009924:Organ Culture Techniques; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley
D000442:Octanols; C067943:2-octanol; D019850:Heptanol