Alpha adrenergic receptors have role in the inhibitory effect of electrical low frequency stimulation on epileptiform activity in rats

Abstract

Aim: Low frequency stimulation (LFS) inhibits neuronal hyperexcitability following epileptic activity. However, knowledge about LFS’ inhibitory mechanisms is lacking. Here, α₁ and α₂ adrenergic receptors’ roles in mediating LFS inhibitory action on high-K⁺ induced epileptiform activity (EA) was examined in rat hippocampal slices.

Materials and methods: LFS (1 Hz, 900 pulses) was applied to the Schaffer collaterals. Whole-cell, patch clamp recording was used to measure changes in CA1 pyramidal neurons’ excitability. By applying high-K⁺ on hippocampal slices, EA was induced, and neuronal excitability increased.

Results: When administered at the beginning of EA, LFS reduced neuronal excitability. In the presence of prazosin (10 µM, an α₁ adrenergic receptor antagonist) and yohimbine (5 µM, an α₂ adrenergic receptor antagonist), LFS’ typically has a restorative impact on EA-induced membrane potential hyperpolarization and spike firing frequency, but this effect was reduced after high-K⁺ washout; These antagonists did not have a significant effect on LFS’ inhibitory action on spike firing during EA.

Conclusion: These findings suggest that LFS’ anticonvulsant effect, on neuronal hyperexcitability following high-K⁺ EA, may be mediated partly through α adrenergic receptors in hippocampal slices.

Keywords:

• Brain stimulation
• epileptiform activity
• hyperexcitability
• CA1 neurons
• α adrenergic receptors

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by a grant #958826 from National Institute for Medical Research Development (NIMAD), Iran and a grant #IG-39709 from Tarbiat Modares University, Tehran, Iran.