Decreased A-currents in hippocampal dentate granule cells after seizure-inducing hypoxia in the immature rat

Authors

  • Bi-Wen Peng,

    Corresponding author
    1. Department of Physiology, Wuhan University School of Basic Medical Sciences, Wuhan, Hubei, China
    • Address correspondence to Bi-Wen Peng, Department of Physiology, School of Basic Medical Sciences, Wuhan University, Donghu Rd185#, Wuhan 430071, Hubei, China. E-mail: pengbiwen@whu.edu.cn and Russell M. Sanchez, Department of Surgery, College of Medicine, Texas A&M Health Science Center, 1901 S. 1st St., Bldg. 205, Temple, TX 76504, U.S.A. E-mail: rsanchez@medicine.tamhsc.edu

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  • Jason A. Justice,

    1. Department of Surgery, College of Medicine, Texas A&M Health Science Center & Central Texas Veterans Health Care System, Temple, Texas, U.S.A
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  • Xiao-Hua He,

    1. Department of Physiology, Wuhan University School of Basic Medical Sciences, Wuhan, Hubei, China
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  • Russell M. Sanchez

    Corresponding author
    1. Department of Surgery, College of Medicine, Texas A&M Health Science Center & Central Texas Veterans Health Care System, Temple, Texas, U.S.A
    • Address correspondence to Bi-Wen Peng, Department of Physiology, School of Basic Medical Sciences, Wuhan University, Donghu Rd185#, Wuhan 430071, Hubei, China. E-mail: pengbiwen@whu.edu.cn and Russell M. Sanchez, Department of Surgery, College of Medicine, Texas A&M Health Science Center, 1901 S. 1st St., Bldg. 205, Temple, TX 76504, U.S.A. E-mail: rsanchez@medicine.tamhsc.edu

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Summary

Purpose

Cerebral hypoxia is a major cause of neonatal seizures, and can lead to epilepsy. Pathologic anatomic and physiologic changes in the dentate gyrus have been associated with epileptogenesis in many experimental models, as this region is widely believed to gate the propagation of limbic seizures. However, the consequences of hypoxia-induced seizures for the immature dentate gyrus have not been extensively examined.

Methods

Seizures were induced by global hypoxia (5–7% O2 for 15 min) in rat pups on postnatal day 10. Whole-cell voltage-clamp recordings were used to examine A-type potassium currents (IA) in dentate granule cells in hippocampal slices obtained 1–17 days after hypoxia treatment.

Key Findings

Seizure-inducing hypoxia resulted in decreased maximum IA amplitude in dentate granule cells recorded within the first week but not at later times after hypoxia treatment. The decreased IA amplitude was not associated with changes in the voltage-dependence of activation or inactivation removal, or in sensitivity to inhibition by 4-aminopyridine (4-AP). However, consistent with the role of IA in shaping firing patterns, we observed in the hypoxia group a significantly decreased latency to first spike with depolarizing current injection from hyperpolarized potentials. These differences were not associated with changes in resting membrane potential or input resistance, and were eliminated by application of 10 m 4-AP.

Significance

Given the role of IA to slow action potential firing, decreased IA could contribute to long-term hippocampal pathology after neonatal seizure-inducing hypoxia by increasing dentate granule cell excitability during a critical window of activity-dependent hippocampal maturation.

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