Impaired firing and sodium channel function in CA1 hippocampal interneurons after transient cerebral ischemia.

Although interneurons in area CA1 of the hippocampus are less vulnerable to cerebral ischemia than CA1 pyramidal cells, it is not clear whether their relatively intact cellular morphology implies preservation of normal function. As maintenance of cellular excitability and firing properties is essential for interneurons to regulate neural networks, we investigated these aspects of interneuronal function after transient cerebral ischemia in rats. Cerebral ischemia in rats was induced for 8 mins by a combination of bilateral common carotid artery occlusion and hypovolemic hypotension, and whole cell patch clamp recordings were made in hippocampal slices prepared 24 h after reperfusion. Interneurons located within stratum pyramidale of area CA1 exhibited normal membrane properties and action potentials under these conditions. However, their excitability had declined, as evidenced by an increased action potential threshold and a rightward shift in the relationship between injected depolarizing current and firing rate. Voltage-clamp experiments revealed that transient cerebral ischemia reduced the peak Na(+) current and shifted Na(+) channel activation to more depolarized values, but did not alter steady-state inactivation of the channel. Double immunofluorescence cytochemistry showed that transient cerebral ischemia also reduced Na(v)1.1 subunit immunoreactivity in interneurons that coexpressed parvalbumin. We conclude that transient cerebral ischemia renders CA1 interneurons less excitable, that depressed excitability involves impaired Na(+) channel activation and that Na(+) channel dysfunction is explained, at least in part, by reduced expression of the Na(v)1.1 subunit. These changes may promote interneuron survival, but might also contribute to pyramidal cell death.