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Inhibition of oxidative metabolism increases persistent sodium current in rat CA1 hippocampal neurons
Author(s) -
Hammarström A. K. M.,
Gage P. W.
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.735bj.x
Subject(s) - oxidative metabolism , hippocampal formation , oxidative phosphorylation , metabolism , chemistry , sodium , neuroscience , endocrinology , biochemistry , biology , organic chemistry
1 Whole‐cell patch‐clamp recordings from freshly dissociated rat CA1 neurons revealed a large transient Na + current ( I Na,T ) and a smaller, inactivation‐resistant persistent Na + current ( I Na,P ). Both currents could be blocked with TTX. 2 The average current densities of I Na,T and I Na,P in thirty cells were 111.0 ± 9.62 and 0.87 ± 0.13 pA pF −1 , respectively. 3 Inhibiting oxidative phosphorylation by adding 5 mM sodium cyanide to the pipette solution significantly increased the amplitude of I Na,P but had no significant effect on the amplitude of I Na,T . 4 Exposing CA1 neurons to hypoxia for more than 7 min caused an increase in the amplitude of I Na,P . There was also a delayed decrease in the amplitude of I Na,T . 5 INa,P was more sensitive to the Na + channel blockers TTX and lidocaine than I Na,T . The IC 50 for the effect of TTX on I Na,P was 9.1 ± 1.2 nM whereas the IC 50 for I Na,T was 37.1 ± 1.2 nM, approximately 4‐fold higher. Lidocaine (lignocaine; 1 μM) reduced I Na,P to 0.24 ± 0.15 of control ( n = 4 ) whereas I Na,T was essentially unaffected (0.99 ± 0.11, n = 4). 6 These results show that I Na,P is increased when oxidative metabolism is blocked in CA1 neurons. The persistent influx of Na + through non‐inactivating Na + channels can be blocked by concentrations of Na + channel blockers that do not affect I Na,T .